Search Results (88)

Newborn screening (NBS) for sickle cell disease (SCD) has been performed in the United States (US) for decades, significantly reducing infant morbidity and mortality. A landmark clinical trial demonstrated that early identification of SCD enabled timely and life-saving prophylactic penicillin; this led to recommendations for universal NBS across the US. Early use of hydroxyurea as a safe and effective treatment for SCD further improved clinical outcomes by preventing acute and chronic disease complications. These advances add to the importance of early diagnosis through NBS, providing an opportunity for early treatment intervention. In recent years, high-resource countries—including those in Europe, the UK, and Canada—have adopted NBS for SCD using diverse strategies. Simultaneously, pilot programs in lower-resource settings such as Africa, Brazil, and India have demonstrated local feasibility and impact through implementation efforts. An overarching equity gap for achieving global NBS for SCD is the variable access to simple, accurate, and affordable testing. Other challenges include timing of NBS testing, targeted populations, laboratory methods, and parental education with genetic counseling. Questions remain about the equitable enrollment of affected infants worldwide into comprehensive care to ensure early treatment. These challenges raise concerns about sustainability, underscore the need for long-term funding and a strategic plan, and highlight persistent inequities from the lack of global NBS standards. Full article

The genus Kalanchoe (Crassulaceae) comprises approximately 125 species of succulents distributed across Madagascar, Africa, Arabia, Australia, Southeast Asia, and tropical America. Traditionally regarded as “miracle plants”, Kalanchoe species are employed for treating inflammatory, infectious, metabolic, and cardiovascular conditions; this is associated with their abundant content of polyphenols, including phenolic acids and flavonoids such as quercetin, kaempferol, luteolin, rutin, and patuletin. However, robust clinical evidence remains limited. This review integrates pharmacological and bioinformatic perspectives by analyzing more than 70 studies published since 2000 on 15 species, including Bryophyllum. As an in silico complement, the genome of Kalanchoe fedtschenkoi was used to predict genes (AUGUSTUS), perform homology searches against Arabidopsis thaliana, and model three key enzymes: CHS, CYP90, and VEP1. The AlphaFold2/ColabFold models showed conserved catalytic motifs, and molecular docking with representative ligands supported the plausibility of biosynthetic pathways for flavonoids, brassinosteroids, and bufadienolides. The available evidence highlights chemopreventive, antibacterial, anti-inflammatory, antiviral, antioxidant, and cytotoxic activities, primarily associated with flavonoids and bufadienolides. Significant gaps remain, such as the lack of gene–metabolite correlations and the absence of standardized clinical trials. Overall, Kalanchoe represents a promising model that requires multi-omics approaches to enhance its phytopharmaceutical potential. Full article

Lecythidaceae species are known worldwide for their ability to produce edible nuts of high nutritional value, such as Brazil nuts, and are also used in traditional medicine in countries across America, Asia, and Africa. The potential of these species has aroused interest in their chemical composition, nutritional properties, and biological activities, with emphasis on anti-inflammatory and antinociceptive actions. The objective of this review was to summarize data regarding the anti-inflammatory and antinociceptive activities of Lecythidaceae species, identify the most promising bioactive agents, and elucidate their potential mechanisms of action. This integrative review was conducted by comprehensively searching the main electronic databases for scientific articles, with no restriction on publication date, that were available in full. Based on this survey, thirty-four articles were identified, covering twelve Lecythidaceae species with anti-inflammatory and antinociceptive actions evaluated in in vitro and in vivo models and randomized clinical trials. Studies encompass extracts, fractions, nuts, and isolated compounds, among which the extracts and fractions of Barringtonia angusta Kurz, Couroupita guianensis Aubl., Lecythis pisonis Cambess., and Petersianthus macrocarpus (P. Beauv.) Liben demonstrated potent inhibition of inflammatory mediators through suppression of gene expression in vitro and in vivo, acting via blockade of the nuclear factor kappa-light-chain-enhancer of activated B cells (KN-κB) signaling pathway. This finding highlights a relevant molecular mechanism by which Lecythidaceae species may exert their anti-inflammatory potential and supports further studies focused on isolating active fractions and elucidating possible synergistic effects. Ethnopharmacological and chemical composition data are also presented and discussed within the scope of their biological applications, highlighting the therapeutic potential of Lecythidaceae species and identifying promising candidates for future development of novel anti-inflammatory phytopharmaceuticals. Full article

Clinical trial (CT) safety surveillance is critical to protecting participants and ensuring reliable evidence on the safety and efficacy of new medical products. This is especially relevant in Africa, where CT activity remains limited, regulatory maturity varies, and drug safety surveillance systems are under-resourced despite considerable demographic advantages and genetic and cultural diversity. Pre-licensure safety monitoring is a vital yet underdeveloped element of the research ecosystem, and the absence of a regional repository for safety data constrains early detection of risks, particularly in multi-country trials. To assess the current state of CT safety surveillance in Africa, a landscape analysis of the systems for clinical trial safety data reporting, collation, and analysis was conducted. Expert perspectives were synthesized to describe existing practices, identify key gaps, and propose opportunities for strengthening systems. Findings revealed limited regulatory capacity, limited drug safety monitoring expertise, and inadequate resources for causality assessment and aggregate data analysis. Despite these challenges, opportunities exist to strengthen CT safety surveillance through digitization of reporting systems, harmonization of serious adverse event forms, regional collaboration, and capacity building for strengthening the ecosystem. Experts emphasized the need for collaboration among regulators of member states, availability of electronic CT management platform in member states and a regional pre-licensure safety data repository to enable timely evidence generation, support member states, and ensure appropriate linkages between pre-licensure and post-market surveillance. Strengthening CT safety surveillance is critical for safeguarding participants, promoting ethical research, and enhancing Africa’s role in global clinical research. The results of this landscape analysis provide a roadmap for building a coordinated model for pre-licensure safety monitoring across the continent. Full article

Colorectal cancer (CRC) is among the most prevalent malignancies worldwide, representing the second leading cause of cancer-related mortality and accounting for approximately 2 million new cases and nearly half a million deaths annually. Global age-standardized incidence rates are highest in Australia/New Zealand and other Western countries, and lowest in parts of sub-Saharan Africa and South Asia, reflecting variations in demographics, lifestyle exposures, and screening practices. Colon cancer constitutes the larger fraction of CRC cases, with rectal cancer contributing substantially, and early-onset CRC (<50 years) is increasing across both high-income and emerging regions. Established risk factors include age, hereditary syndromes, obesity, sedentary behavior, dietary patterns, metabolic disorders, and chronic inflammation, with notable distinctions between colon and rectal subsites. This narrative review provides a comprehensive overview of CRC epidemiology, molecular and genetic pathogenesis, staging, and modern therapeutic approaches, addressing colon and rectal cancers separately due to their distinct biology, clinical behavior, and treatment strategies. By integrating current knowledge on genetic drivers, systemic and local therapies, and patient stratification, the review aims to inform clinical practice, support clinical trial design, discuss ongoing challenges and future perspectives, and foster further research toward precision-guided management of CRC. Full article

In Africa, the folkloric practices involving plant-based remedies play a crucial role in livestock farming, often attributed to the limited access to modern veterinary services. The use of Acacia species (including those reclassified as Vachellia species) in ethnoveterinary medicine has garnered increasing interest due to their high protein content and medicinal (including anti-parasitic) properties, offering a sustainable source of fodder particularly in arid and semi-arid regions. However, scientific assessment of their efficacy and safety remains limited. This systematic review examines the ethnoveterinary uses, biological efficacy and safety of Acacia species across Africa. A literature search was conducted using PubMed, Google Scholar and Scopus, yielding 519 relevant studies published between 2001 and 2024. After applying the inclusion and exclusion criteria, 43 eligible studies were analyzed based on their relevance, geographical location and livestock disease applications. Plants of the World online database was used to validate the names of the species and authority. Ethiopia had the highest usage of Acacia species (25%), then Nigeria (20%) followed by both South Africa (15%) and Namibia (15%). Vachellia nilotica (Acacia nilotica) was the most frequently cited species (26.3%), followed by Vachellia karroo (Acacia karroo) (15.8%). Ethnobotanical records indicate that the different Acacia species have been traditionally used to treat conditions such as diarrhea, wound infections and complications such as retained placenta. Pharmacological studies corroborate the therapeutic benefits of Acacia species with evidence of their antimicrobial, anti-inflammatory, antioxidant and anthelmintic effects, though some toxicity concerns exist at high dosages. The systematic review revealed the efficacy and safety (to some extent) of Acacia species in livestock disease management, emphasizing their potential integration into veterinary medicine. However, the dearth of in vivo studies underscores the need for pre-clinical and clinical trials to establish safe and effective dosages for use in livestock. Full article

Current estimates suggest that Africa contains about 14% of the world’s population and accounts for 20% of the global burden of disease. Yet, it accounts for a mere 3% of clinical trials globally. The time is ripe—even overdue—for determining how best to direct future health research efforts. In response, a call has been heard for a continent-wide Africa-centric research ethics framework to redirect health research in Africa, as well as address the health research ethics malpractices that have violated the rights, dignity and well-being of participating African communities. Nevertheless, we should remain aware of what already exists and what continues to be of value. Creating parallel frameworks risks fragmentation of research, increased costs in having to meet differing requirements and delayed access of patients to new treatments. Existing international consensus documents which have evolved and been fine-tuned over time, offer guidance for ensuring ethical instigation and management of health research. The Declaration of Helsinki enunciates clear principles for ensuring the ethical conduct of clinical research, while CIOMS’ 2016 International Ethical Guidelines for Health-related Research involving Humans offer guidance for implementing these principles. It is failure to apply existing ethical principles and guidance—and not any perceived inadequacy of those principles—that has resulted in sub-optimal protection of African research participants. Full article

Background: The COVID-19 pandemic highlighted the need for innovative vaccine platforms that elicit durable immunity. Self-amplifying RNA (saRNA) vaccines offer rapid production and dose-sparing advantages over traditional mRNA platforms. In Uganda’s first SARS-CoV-2 vaccine trial (NCT04934111), we assessed the safety and immunogenicity of a saRNA vaccine encoding the SARS-CoV-2 spike (S) glycoprotein in seronegative and seropositive adults. Methods: This non-randomised phase 1 trial (December 2021–April 2022) enrolled 42 healthy adults (18–45 years), including 12 seronegative and 30 seropositive for SARS-CoV-2. Participants received two 5 μg doses of saRNA vaccine, four weeks apart. Reactogenicity was assessed using diary cards for seven days post-vaccination, and adverse events were monitored throughout the 24-week study. Binding and neutralising antibody levels were quantified using ELISA and pseudovirus neutralisation assays. Findings: The vaccine was well tolerated, with only mild-to-moderate adverse events, including fatigue, headache, and chills. No serious vaccine-related events occurred. Among seronegative participants, 91.6% seroconverted after two doses (median S-IgG: 3695 ng/mL, p < 0.001). In the seropositive participants, S-IgG rose modestly from 7496 to 11,028 ng/mL after the second dose. Neutralising titres increased modestly across WT, BA.2, and A.23.1 variants, with no significant differences between groups. Conclusion: The saRNA SARS-CoV-2 vaccine was safe and immunogenic, inducing robust spike glycoprotein-specific antibody responses, particularly in seronegative participants. This trial demonstrates the potential of saRNA vaccines for broader use. Full article

Background: The recent global outbreak with clade IIb and the concurrent emergence of clade I mpox virus in Africa show that mpox is a challenging problem. MVA-BN induces low-level mpox-neutralizing antibody responses that wane rapidly. This study was conducted to compare the mpox immunity induced by a replication-competent smallpox vaccine and non-replicating MVA-BN. Methods: Stored sera (n = 302) and PBMCs (n = 244) collected pre-vaccination and at five post-vaccination time points in MVA-BN and six post-vaccination time points in Dryvax clinical trials were used. Antibody titers that neutralized at least 50% of mpox in cell culture were determined by the focus reduction neutralization test (FRNT) 50, and the mpox-specific T cell responses were measured using an IFN-γ ELISPOT assay. Results: The peak geometric fold rise (95% CI) (i.e., the maximum GMFR across all study visits) in the mpox FRNT50 for subcutaneous (SC) MVA-BN, intradermal (ID) MVA-BN, and Dryvax was 22.1 (8.3, 59.1), 18.5 (8.0, 43.1), and 245.8 (100.4, 601.6), respectively. The GMFR at day 180 post-vaccination for MVA-BN (SC), MVA-BN (ID), and Dryvax was 2.4, 2.7, and 64, respectively. The mean (95% CI) peak number of mpox-specific IFN-γ-producing SFCs was 127 (43.1, 238.3), 87.3 (46, 137), and 61.2 (44.3, 77.7) for MVA-BN (SC), MVA-BN (ID), and Dryvax, respectively. On day 180, the mean SFCs in the three groups decreased to 10.8 (−34.4, 3.8), 3.3 (−6.2, 18.6), and 2.2 (−9, 12.5), respectively. Conclusions: The peak mpox-neutralizing antibody titer was >10-fold lower in MVA-BN recipients compared to those who received a replication-competent smallpox vaccine, and the level at day 180 was >20 times lower in MVA-BN recipients. MVA-BN induced similar or higher T cell responses. Full article

Background: Vaccine research publications play a crucial role in the scientific process by strategically linking the generation of knowledge with its translation into vaccine policy and practice. This study was designed to understand vaccine and immunization research publication trends in Africa to inform strategic directions for vaccine research and innovation efforts in the continent. Methods: We searched PubMed only for vaccine and immunization-related publications from Africa between 1 January 2016 and 8 August 2024. Metrics such as annual growth rates, geographical distribution, international collaboration, and trend topics were analyzed. We conducted separate analyses for general vaccine research, vaccine clinical trials, and vaccine evidence syntheses (systematic reviews and meta-analyses). Results: Vaccine research in Africa demonstrated an annual growth rate of 55.4% (based on the 10,000 records retrieved due to PubMed’s export limit), while vaccine trials saw a decline of 6.08% during the study period. The trend topics analysis across vaccine research, trials, and reviews showed that topics shifted from a focus on general vaccine development, immunization, and malaria pre-2020 to COVID-19-related topics in 2020, with post-2020 research returning to traditional topics like immunization schedules, vaccine safety, and pediatric and maternal vaccines. Additionally, the COVID-19 pandemic had a profound impact on vaccine research, leading to a surge in publications for vaccine research, trials, and reviews. About 65.8% of vaccine research featured international co-authorship. Vaccine trials had a higher rate of international co-authorship at 79.8%. Conclusion: While vaccine research in general in Africa has increased, vaccine trials do not match this increase. The number of clinical trials remained relatively stagnant, reflecting ongoing challenges in the vaccine research ecosystem, particularly in building and sustaining clinical trial capacity across the region. In addition, disparities in research productivity exist between countries. Research prioritization, strategic collaborations, capacity building for research, and improved research infrastructure require critical consideration. Full article

Background/Objectives: Following previous successful Phase I clinical trials conducted in men and women in a non-endemic area for schistosomiasis in Brazil, the Sm14 vaccine was evaluated in an endemic region in Senegal. We report successful clinical trials in adults (Phase IIa) and school children (Phase IIb), respectively, of a Schistosoma mansoni 14 kDa fatty acid-binding protein (Sm14) vaccine + a glucopyranosyl lipid A (GLA-SE) adjuvant. Methods: Participants were evaluated based on clinical assessments, laboratory tests (including hematologic and biochemical analyses of renal and hepatic functions), and immunological parameters (humoral and cellular responses) up to 12 months after the first vaccination dose in the Phase IIa trial and after 120 days in the Phase IIb trial. Results: The results showed strong immunogenic responses and good tolerance in both adults and children, with no major adverse effects. Importantly, significant increases in Sm14-specific total IgG (IgG1 and IgG3) were observed as early as 30 days after the first vaccination, with high titres remaining at least 120 days afterwards. Sm14-specific total IgG serum levels were also significantly enhanced in adults and in both infected and non-infected, vaccinated children and elicited robust cytokine responses with increased TNFα, IFN-γ, and IL-2 profiles. Conclusions: Overall, the Sm14+GLA-SE vaccine is safe and highly immunogenic, with a clearly protective potential against schistosomiasis, supporting progression to the next Phase III clinical trials. Full article

Background/Objectives: Although the COVID-19 pandemic has largely concluded, the varied trajectories it has followed in different regions of the world remain incompletely understood. Intensive research is needed to fully grasp its course and the implications for future global health challenges. Notably, the milder trajectory of the COVID-19 pandemic in Sub-Saharan Africa has defied initial predictions. An emerging body of evidence suggests that, in addition to the continent’s younger average age and the lower prevalence of relevant comorbidities, co-infections with helminths may have also impressively shaped the pandemic’s milder trajectory in the region. Indeed, helminths are renowned for their ability to modulate human immune responses, which, while potentially beneficial in limiting excessive inflammation, could also diminish vaccine efficacy and impede viral clearance. This study investigated different aspects of the intricate interactions between COVID-19 and Lymphatic Filariasis (LF), a helminth infection caused by parasitic worms such as Wuchereria bancrofti, Brugia malayi, and Brugia timori and endemic to various regions in Sub-Saharan Africa and the tropics. Methods: For this purpose, samples of a larger and ongoing clinical trial (ethical approval codes: CHRPE/AP/525/17 and 325/21; trial registration number ISRCTN14042737) were collected from 222 individuals from endemic areas of Ghana, along with comprehensive clinical and demographic data. The samples include LF patients (n = 222) grouped according to their Lymphoedema (LE) stages, as well as COVID-19 vaccinated (n = 81) and non-vaccinated individuals (n = 141). All vaccinated participants received the COVID-19 vaccine ChAdOx1-S (also known as Vaxzevria) developed by the University of Oxford and AstraZenca. The expressions of SARS-CoV-2 and filarial-specific antibodies (IgG, IgA) were accessed using ELISA, while Luminex-based immunoassays were employed to measure the expression of SARS-CoV-2 variant-specific neutralizing antibodies. The interplay between vaccine responses and demographic factors was analyzed using group comparisons with the Kruskal-Wallis or Mann-Whitney U tests. Results: The results indicate that a remarkable portion of unvaccinated individuals (56% IgA seropositive, 39% IgG seropositive) developed antibodies against SARS-CoV-2 despite no confirmed infection. Notably, the study identified a robust antibody response to COVID-19 vaccination, which was independent of the degree of LF pathology or parasitic status. An important observation was the reduced SARS-CoV-2 antibody response in individuals seropositive for Ascaris lumbricoides (p = 0.0264), highlighting an interaction between roundworm infection and COVID-19. Conclusions: The study concludes that the ChAdOx1-S COVID-19 vaccine (AstraZeneca) triggers a strong immune response in LF patients; however, filarial and/or soil-transmitted helminth seropositivity might influence the COVID-19 infection-induced response. These findings emphasize the complexity of infectious disease dynamics in co-infected populations and the need to decipher parasite-induced immunomodulatory mechanisms on COVID-19 vaccination. Full article

The rVSVΔG-ZEBOV-GP vaccine demonstrated efficacy in preventing Ebola virus (EBOV) disease in a ring vaccination clinical trial conducted during the 2014–2016 West Africa outbreak and is licensed by regulatory agencies, including the US FDA and the EMA. Here, we present two studies that evaluated the durability of immunogenicity and protection from an EBOV challenge up to ~12 months following vaccination with rVSVΔG-ZEBOV-GP in nonhuman primates (NHPs). Cynomolgus macaques were vaccinated with either one or two doses of rVSVΔG-ZEBOV-GP or a saline control and were challenged intramuscularly with EBOV at a target dose of 1000 pfu at ~4 months (Study 1) or ~8 or ~12 months (Study 2) after the last vaccination. All vaccinated animals developed robust ZEBOV-GP-specific IgG and neutralizing antibody titers, which were sustained until the last time point tested prior to the challenge. The majority of animals (88–93%) challenged with EBOV at ~4 or ~8 months post-vaccination survived, whereas the survival rate was lower (53%) in animals challenged ~12 months post-vaccination. These results demonstrate that both one-dose and two-dose regimens of the rVSVΔG-ZEBOV-GP vaccine induced durable ZEBOV-GP-specific antibody titers in NHPs and provided high levels of protection against a lethal EBOV challenge up to ~8 months post-vaccination. In this stringent challenge model, decreased protection was observed at ~12 months post-vaccination despite sustained antibody levels. Full article

Maytenus senegalensis (Lam.) Excell, also known as Gymnosporia senegalensis (Lam.) Loes, is distributed particularly in savannah regions of tropical Africa. It is used to treat malaria, tuberculosis, rheumatism and diarrhea, amongst other afflictions. The objective of this comprehensive review is to summarize studies on phytochemistry, molecular docking, pharmacology, toxicology, ethnopharmacology, botany, and clinical trials of M. senegalensis. Data on M. senegalensis were collected using different databases such as Google Scholar, Science Direct, Web of Science, Scopus, SciFinder, Wiley Online, etc. This review showed that 118 biomolecules from different parts of M. senegalensis were identified. A total of 46 compounds were tested for antiplasmodial, anti-inflammatory, and antiproliferative activities, and some in vivo studies were carried out on mice. Isomintlactone (31), pristimerin (24), and jacareubin (32) were analyzed for molecular docking. The crude extracts and fractions had pharmacological activities, including antiparasitic, antimycobacterial, anti-inflammatory, antiviral, antiproliferative, and antidiabetic, while showing low toxicity in mice. Clinical trial studies on the safety and tolerability of M. senegalensis ethanol root bark extracts in male volunteers showed its potential immunomodulatory effects. Another trial specifically evaluated the electrocardiographic effects of M. senegalensis in adult volunteers and showed its advantageous cardiac profile by improving the overall safety profile. Full article

Background: HIV-1 envelope (Env) variable loops 1 and 2 (V1V2) directed non-neutralizing antibodies were a correlate of decreased transmission risk in the RV144 vaccine trial. Thus, the elicitation and breadth of antibody responses against the V1V2 of HIV-1 Env are important considerations for HIV-1 vaccine candidates. The V1V2 region’s highly variable nature and the extensive diversity of subtype C HIV-1 Envelopes (Envs) make the V1V2 response breadth a high priority for HIV-1 vaccine regimens aiming for V1V2-mediated protection in Southern Africa. Here, we determined whether the breadth of the anti-V1V2 vaccine response can be broadened by including HIV-1 Env strains computationally designed to enhance the coverage of subtype C V1V2 sequence diversity. Methods: Three subtype C Env strains were selected to maximize antibody binding coverage while complementing subtype C vaccine gp120s that were given in human clinical trials in South Africa, as well as to improve epitope accessibility. Humoral immunogenicity of a novel trivalent gp120 vaccine immunogen, a bivalent gp120 boost already in clinical trials (1086C and TV1), and a pentavalent (all five gp120s combined) were evaluated in a preclinical immunization study in guinea pigs. The pentavalent combination was further evaluated with alum versus glucopyranosyl lipid adjuvants formulated in squalene-in-water emulsion (GLA-SE) adjuvants in non-human primates. The breadth of the anti-V1V2 response was assessed using an array of cross-subtype variable loops 1&2 (V1V2) scaffold proteins and linear V2 peptides. Results: The breadth of the IgG response against V1V2 antigens of the trivalent and pentavalent groups was comparable, and both were greater than the breadth of the bivalent group. Linear epitope mapping showed that two linear epitopes in V2 were targeted by the vaccinated animals: the V2 hotspot focused at ¹⁶⁹K that potentially correlated with decreased HIV-1 risk in RV144 and the V2.2 site (¹⁷⁹LDV/I¹⁸¹) that is part of the integrin α4β7 binding site. The bivalent vaccine elicited a significantly higher magnitude of binding to the V2 hotspot compared to the trivalent vaccine whereas the trivalent vaccine elicited significantly higher binding to the V2.2 epitope compared to the bivalent vaccine, while the pentavalent recognized both regions. Conclusions: These results demonstrate that the three new computationally selected subtype C Envs successfully complemented 1086C and TV1 for broader V1V2 antibody responses, and, in concert with adjuvants that stimulate V1V2 responses, can be considered as part of a rationale immunogen design to improve V1V2 IgG coverage in future vaccine trials in South Africa. Full article