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RhD alloimmunization in pregnancy and hemolytic disease of the fetus and newborn in Africa: A systematic review and meta-analysis
Full text linkAlthough hemolytic disease of the fetus and newborn (HDFN), caused by maternal alloimmunization against fetal erythrocytes, has been nearly eliminated in high-income settings, it likely remains a significant public health problem in low-resource settings in Africa and elsewhere. We performed a comprehensive literature review across six major databases to determine the proportion of RhD-negativity, anti-D immunoprophylaxis utilization, RhD-alloimmunization prevalence, and the burden of RhD-mediated HDFN among pregnant women in Africa. A random-effects model was used to determine pooled estimates. We included 74 studies from 17 countries (42 from Nigeria), published between 1960 and 2024, involving 245,046 pregnancies, mostly from tertiary centers. The proportion of RhD negativity was 4.8 % (95 % CI: 4.1–5.7 %). The proven RhD alloimmunization rate was 5.8 % (95 % CI: 4.1–8.2 %). In multigravida women, the proportion of RhD alloimmunization was 5.7 % (95 % CI: 3.1–10.4 %). Anti-D immunoprophylaxis utilization after a previous pregnancy, reported in 18 studies (1490/3756 women), was 29.7 % (95 % CI: 18.0–45.0 %), with no effect on alloimmunization rate. Nine studies (including 50 neonates from 168 alloimmunized women) provided data on HDFN, with a pooled prevalence of 36.2 % (95 % CI: 16.8–61.4 %). In many papers, the specificity of the alloantibodies was not determined. Data on gravidity and the clinical definition of HDFN were incomplete. We conclude that there is a lack of robust data from Africa, thereby hampering HDFN prevention efforts. To eliminate HDFN in Africa, integrated strategies are urgently needed, including universal RhD typing and antibody screening, access to polyclonal anti-D immunoprophylaxis, and population-based surveillance.</p
Implementation strategies and outcomes of intravenous iron use for treatment of anaemia during and after pregnancy in low- and middle-income countries: A scoping review
Full text linkThere is sufficient evidence of the efficacy of Intravenous (IV) over oral iron in treating anaemia in pregnancy and postpartum. However, poor implementation can lead to little or no benefit. The objectives of this scoping review are to map and synthesise evidence related to implementation strategies and implementation outcomes of IV iron use for treating anaemia in pregnancy and the postpartum in low- and middle-income countries (LMICs). This scoping review was conducted in accordance with the Joanna Briggs Institute’s methodology for conducting scoping reviews. Electronic databases were searched to identify relevant literature sources published up until June 2025. Two independent reviewers conducted screening using the Covidence software. Descriptive statistics was used to synthesise data and findings were reported narratively. Synthesis of implementation strategies was guided by the Expert Recommendations for Implementing Change compilation. Our search yielded 4,589 publications, 20 were included in the review. Ten studies used implementation strategies, mostly “assessment for readiness and identification of barriers and facilitators” (40%; 4/10) and “promotion of adaptability” (30%; 3/10). Fourteen studies mentioned the assessment of implementation outcomes; most assessed were acceptability (42.9%; 6/14) and fidelity (35.7%; 5/14). Only five studies used any theory, model, framework (TMF) or validated measures in the implementation of strategies or assessment of outcomes. In conclusion, there is limited implementation research on the use of IV iron for the treatment of anaemia in pregnancy and the postpartum in LMICs. Critically, the use of TMFs and validated measures are deficient in current sources of evidence. More rigorous assessments of the implementation of IV iron for obstetric anaemia in LMICs are required to guide practice, policy and uptake
Genetic Surveillance Reveals Differential Evolutionary Dynamic of Anopheles gambiae Under Contrasting Insecticidal Tools Used in Malaria Control
No full textMalaria, a febrile disease caused by the Plasmodium parasites and transmitted by mosquitoes, is a leading cause of mortality in children under 5 in endemic countries. The widespread deployment of insecticide-treated bed nets (ITNs) has significantly reduced malaria transmission, but rising levels of insecticide resistance threaten to halt the progress. Monitoring insecticide resistance is vital for effective vector control, particularly when deploying new tools. Understanding mosquito population responses to these interventions is crucial for guiding control programmes in making informed decisions about the selection, timing and geographic deployment of tools. This genomic study investigates the demographic and evolutionary consequences on the malaria vector Anopheles gambiae of deploying standard ITNs (containing only pyrethroids) and pyrethroid-PBO nets (containing pyrethroids plus the synergist piperonyl butoxide) during a clinical trial in Uganda. Despite substantial reductions in indoor mosquito densities in the clinical trial, estimates of nucleotide diversity (π) and linkage disequilibrium revealed no significant decline in effective population size, reflecting continued large population size even after effective control. Marked allele frequency shifts at resistance-associated loci indicated strong selection pressures driven by the interventions, with distinct selective dynamics between the two net types, highlighting alternative pyrethroid detoxification pathways in the presence of PBO. A duplication in the Cyp9k1 gene significantly increased in frequency in populations exposed to pyrethroid-only nets but decreased in populations exposed to PBO-treated nets, suggesting that selection for over-expression of this gene is removed when this resistance mechanism is impacted by PBO. An alternative potential detoxification mechanism was selected within a region of the 2La chromosomal inversion on chromosome 2 L, which encompasses the UDP-glucose 6-dehydrogenase gene. This variant consistently increased in frequency when exposed to PBO-treated nets. Additionally, pyrethroid-only nets selected for a novel locus on the X chromosome containing the diacylglycerol kinase gene, which is potentially linked to behavioural adaptations through its role in neurotransmission modulation. Our findings underscore the importance of genomic surveillance in vector control, revealing distinct evolutionary dynamics of insecticide resistance mechanisms in the presence of PBO. While ITNs remain effective, the persistence and evolution of resistance-associated alleles highlight the need for adaptive and dynamic resistance management strategies. By integrating high-resolution genomic data with epidemiological and entomological monitoring, this study offers actionable insights to sustain malaria control efforts amid the ongoing challenge of insecticide resistance.</p
Exploring the larvicidal and repellent potentials of silver nanoparticles greenly synthesized using three Congolese plant extracts against Anopheles gambiae along with molecular docking analysis
Full text linkChemical larvicides and repellents have long been used to combat Anopheles gambiae, the primary malaria vector. However, their prolonged application has raised significant concerns regarding environmental toxicity, human health risks, and the emergence of resistant mosquito populations. This study presents a sustainable alternative consisting of green-synthesized silver nanoparticles (AgNPs) derived from Lippia multiflora, Ocimum gratissimum, and Tetradenia riparia. These nanoparticles were characterized using several techniques, including UV–visible spectrophotometry, transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDX) and Fourier transform infrared (FTIR) spectroscopy, revealing their spherical structure with diameters of 20–50 nm and stabilization by plant secondary metabolites. Aqueous suspensions of AgNPs derived from these three plants demonstrated dose-dependent larvicidal efficacy, achieving up to 95% mortality, while creams containing AgNPs from Lippia multiflora and Ocimum gratissimum exhibited an impressive 85% repellent efficiency. Molecular docking studies revealed that secondary metabolites used as capping agents enhanced larvicidal activity by inhibiting angiostensin converting enzyme of Anopheles gambiae (AnoACE2), further demonstrating the synergistic role of these metabolites in stabilising and boosting AgNPs efficacy. These findings highlight the potential of green-synthesized AgNPs as an eco-friendly and effective alternative to conventional chemical larvicides and repellents, addressing a pressing global need for sustainable mosquito control strategies. By leveraging the bioactivity of plant-derived compounds, this approach minimises environmental and health risks while offering high efficacy against malaria vectors. This research underscores the significant role of green nanotechnology in developing innovative solutions to vector control, paving the way for its integration into holistic malaria prevention programs and the fight against other mosquito-borne diseases.</p
Low-dose rivaroxaban plus antiplatelet therapy for symptomatic intracranial atherosclerotic stenosis A prospective cohort study
Full text linkBackground: The antithrombotic strategies for symptomatic intracranial atherosclerotic stenosis (sICAS) remains challenging. Dual pathway inhibition (DPI) has demonstrated clinical benefit in coronary and peripheral artery disease. Aims: This study aimed to evaluate the efficacy of DPI with low-dose rivaroxaban plus antiplatelet therapy (APT) compared with APT alone on recurrent stroke with sICAS. Methods: This prospective cohort study included patients with sICAS identified from the Ischemic Cerebrovascular Disease Database of the First Affiliated Hospital of Zhengzhou University between January 2019 to August 2023. Low-dose rivaroxaban was prescribed off-label to patients in the DPI group. The outcomes were ischemic stroke, transient ischemic attack (TIA), acute coronary syndrome (ACS), all-cause death and cardio-cerebrovascular death within 1 year of discharge. Cox regression with inverse probability of treatment weighting (IPTW) was applied to compare outcomes between the DPI and APT groups. The win-ratio method was used to assess the major adverse cardiovascular events (MACE), prioritized in the order of all-cause death, recurrent ischemic stroke or TIA, and ACS. Results: Among the 1217 patients with sICAS, 131 (10.8%) received DPI therapy. The recurrence rate of ischemic stroke was lower in the DPI group compared to the APT group (8/131 [6.1%] vs 136/1086 [12.5%]). DPI significantly reduced the risk of ischemic stroke recurrence (HR = 0.46, 95% CI: 0.23–0.94, p = 0.034) and the incidence of MACE (HR = 0.53, 95% CI: 0.29–0.97, p = 0.041) during the 1-year follow-up, consistent with the IPTW-based cohort (HR = 0.35, 95% CI: 0.16–0.76, p = 0.008; HR = 0.43, 95% CI: 0.22–0.83, p = 0.012). The win-ratio analysis of MACE favored DPI therapy (win ratio = 2.34, 95% CI: 1.41–3.90, p = 0.001). Symptomatic intracranial hemorrhage, fatal bleeding, and hospitalization for gastrointestinal bleeding were infrequent in this cohort. Conclusions: DPI therapy may be associated with a lower risk of recurrent stroke compared with antiplatelet therapy alone in patients with sICAS. These findings warrant further investigation through large-scale randomized controlled trials.</p
Availability, acceptability and adoption of decision aids for HIV prevention and contraception for young people a scoping review protocol
Full text linkINTRODUCTION: Young people face challenges in accessing information on HIV and sexual and reproductive health services, with corresponding suboptimal uptake. Decision aids can provide information and decisional support to improve young people's engagement with health interventions. However, they have not been widely implemented among young people. The availability of different choices for HIV and pregnancy prevention means that it is important to implement interventions that facilitate informed choices for these methods. We describe a protocol for a scoping review that aims to explore the availability, acceptability and use of decision aids for HIV prevention and contraception for young people. METHODS AND ANALYSIS: We will identify relevant studies from the following electronic databases from inception to current date: PubMed, Scopus and Global Health; and grey literature databases, namely medRxiv and Open Access Theses and Dissertations. Eligible studies will report on HIV prevention and/or contraception decision aids and be written in English. Data extraction will be done by two reviewers independently using templates, with discrepancies resolved by consensus. Analysis will be done narratively, and separate for HIV prevention and contraception decision aids. Analysis will also include determination of the suitability of each decision aid for use by young people aged 15-24 years. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews will be employed to present results. ETHICS AND DISSEMINATION: This review does not require ethics approval. The findings from this work will be disseminated through peer-reviewed publications and presentations at local and international conferences. </p
Immune dysregulation through longitudinal lymphocyte trajectories and their clinical determinants in hospitalized COVID-19 patients
No full textObjective: Immune dysregulation plays a pivotal role in the pathophysiology of sepsis and COVID-19, with lymphopenia emerging as a consistent marker of severity and poor prognosis. However, most existing studies have assessed lymphocyte counts at isolated time points, limiting insights into their temporal behavior and prognostic value. The dynamics of lymphocyte recovery or persistence of lymphopenia remain largely unexplored in large populations, as well as the impact of adjunctive therapies such as corticosteroids. We hypothesized that the persistence or recovery of lymphopenia may be key to understanding disease progression and predicting outcomes. Using the multinational ISARIC cohort, we investigated longitudinal lymphocyte trajectories in hospitalized patients and the clinical determinants associated with their evolution over time. Methods: We conducted a multinational prospective observational cohort study using data from the ISARIC-WHO Clinical Characterization Protocol. Patients with confirmed SARS-CoV-2 infection and at least four lymphocyte measurements during the first 28 days of hospitalization were included. We analyzed lymphocyte trajectories, Cox regression survival analyses and multivariable linear regression modelling. We also applied multistate models and joint modeling to assess the association between lymphocyte trajectories and 28-day mortality, incorporating corticosteroid use as a time-varying covariate. Results: Of 945,317 screened patients, 231,933 hospitalized adults with confirmed COVID-19 and sufficient lymphocyte data were included, with 56.6% classified as lymphopenic. Lymphopenia was independently associated with higher rates of ICU admission, organ support, and in-hospital mortality (OR = 1.52, 95% CI 1.48–1.55), and lower absolute lymphocyte counts were strongly linked to worse survival in adjusted Cox models (HR = 1.33 per 1 × 10⁹ cells/L decrease, 95% CI 1.28–1.38). Multistate modeling revealed that lymphopenic patients had a significantly higher daily transition rate to death and a shorter duration in that immune state, while corticosteroid exposure was associated with an increased likelihood of entering and remaining in lymphopenia. Joint modeling identified age, sex, and corticosteroid use as significant predictors of lower lymphocyte trajectories over time, with distinct dynamics between survivors and non-survivors. Conclusion: Lymphopenia was common and strongly associated with worse outcomes in hospitalized COVID-19 patients, with impaired recovery particularly evident in those receiving corticosteroids. These findings highlight the value of lymphocyte monitoring to inform tailored immunomodulatory strategies in sepsis and severe viral infections.</p
Advancing functional and systemic integration of HIV prevention into public health systems
No full textThe global HIV response has delivered substantial progress, largely through vertical programmes that created parallel systems of financing, governance, and service delivery. Sustaining these gains requires embedding HIV prevention more fully within routine public health systems, particularly as external funding declines and health priorities evolve. This Series paper examines how the principal functions of HIV prevention-risk-based prioritisation, demand generation, quality service provision, and continuity of use-are grounded in long-standing public health principles and essential functions. By tracing these shared roots, we show that integration is not an abandonment of HIV prevention's distinctive achievements but an evolution towards more coherent and sustainable public health systems. Although integration moves HIV prevention beyond exceptionalist approaches, it should be understood as an advance that reinforces durability and equity rather than a compromise that dilutes past gains. Drawing on literature, expert consultations, and country experiences, we compare HIV prevention functions against frameworks, such as WHO's Essential Public Health Functions. This comparison highlights integration as a technically sound and conceptually coherent path and acknowledges the financial, political, and structural legacies of vertical programming. We conclude that system-level integration can sustain HIV outcomes and strengthen overall health system resilience.</p
Genetic divergence and lower frequencies of insecticide resistance markers in the novel Anopheles gambiae Bissau molecular form in The Gambia
Full text linkThe members of Anopheles gambiae species complex are ubiquitous in Afro-tropics. They have been exposed continuously to insecticides, contributing to evolution of resistance within the complex. This study used whole genome sequence data from phase 3 of the An. gambiae 1000 Genomes Project to investigate the population structure and resistance mechanisms of a newly identified species, An. gambiae Bissau molecular form (Bissau) in The Gambia. Bissau exhibited subtle divergence from sister taxa An. coluzzii (Fixation index (FST) of 0.013) and An. gambiae s.s. (FST of 0.023), suggesting ongoing geneflow among them. It also displayed a low but evident level of sub-clustering correlating with geographical location, contrary to sister taxa whose populations were not spatially structured. Additionally, Bissau displayed a higher number of substitutions, though at very low frequencies, in target site regions (specifically Vgsc and Ace-1) of the genome compared to its sister taxa. The well-established Vgsc-L995F mutation, normally associated with dichloro-diphenyl-trichloroethane (DDT) and pyrethroid resistance, was detected in all taxa. Also present, but at a lower frequency (< 20%) was N1570Y allele, normally associated with increased level of pyrethroid resistance when it co-occurs with L995F. Additionally, variants T791M and A1746S were found to occur alongside L995F in Bissau population at an elevated linkage disequilibrium (LD r2 = 0.7). These findings accentuate the critical role this novel species could play on the emergence and spread of insecticide resistance in The Gambia.</p
Start4All protocol for a Bayesian cost-effectiveness model of tuberculosis screening and diagnosis in seven high burden low-income and middle-income countries
Full text linkINTRODUCTION: High costs of screening and diagnostic tests remain a major barrier to timely tuberculosis (TB) identification in resource-limited settings. Evidence on the cost-effectiveness of scalable screening algorithms is limited. Start4All is a research project aimed at developing and evaluating algorithmic approaches to TB screening and diagnosis, with the goal of optimising technical and allocative efficiency when expanding diagnostic coverage to primary healthcare and community settings. METHODS AND ANALYSIS: Five screening and diagnostic tests will be evaluated: a capillary blood-based assay (C-reactive protein (CRP)), sputum-based rapid molecular tests (PCR; individual and pooled Xpert MTB/RIF Ultra assay (Xpert Ultra, Cepheid®, California, USA)), a lateral-flow urine-based test for lipoarabinomannan (LF-LAM), and digital chest X-rays with artificial intelligence-based computer-aided detection (CXR-CAD). A microbiological reference standard of positive culture using the mycobacteria growth indicator tube will be used to confirm TB disease. We will compare the cost and effectiveness of concurrent and sequential positive serial combinations (screening algorithms) of CRP, CXR-CAD, LF-LAM, individual and pooled Xpert Ultra. Diagnostic performance will be estimated using sensitivity, specificity, predictive values and proportions of positive results, with Bayesian inference used to derive these estimates. The analysis will include adults (15 years and older) only and will be stratified by HIV status and level of care, including facility and community-based case finding. Effectiveness will be assessed based on the number of people with TB detected. Cost analysis will be conducted from the provider perspective, incorporating commodity and implementation costs. A decision tree model will be developed to assess the cost per number of persons with confirmed TB detected across all countries. Probabilistic sensitivity analysis will be conducted to account for uncertainty in model parameters, incorporating willingness-to-pay and willingness-to-accept thresholds. ETHICS AND DISSEMINATION: WHO ethical review committee approval ERC.0003921. Data will be available on reasonable request to the principal investigator of the consortium. </p