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Global HIV prevention is not on track:how a health systems approach can promote sustainable progress in African countries
No full textThe expansion of the global HIV response has led to substantial reductions in mortality and new infections over the past two decades. Yet, despite these gains, rates of new HIV infections remain much higher than projected, resulting in long-term consequences for controlling the epidemic. Challenges include siloed delivery approaches shaped by the demands and priorities of external funding, lack of integrated data systems for prevention, unaddressed structural risks, and limited community and multisectoral engagement. There is substantial concern that the inability of health systems to consistently reach vulnerable groups, especially with extraordinarily effective new biomedical tools, threatens the long-term control of the HIV epidemic. In this framing paper (the first paper in a six-part Series), we argue that countries that have adopted (or are planning to adopt and invest in) a more integrated health systems approach to the HIV response will be better able to achieve sustainable prevention outcomes and withstand external funding shocks. Focusing on sub-Saharan Africa, we examine current systemic barriers, the risks of continued fragmentation of programmes and accountability, and opportunities to realign HIV programmes—that will be explored thoroughly in the other papers in this Series—through a focus on strengthened governance, a decentralised health systems approach, community engagement, and strengthened pathways for new product introduction and scale-up.</p
Human dimension of urban flood risk and informal resilience in Peshawar, Pakistan
Get PDFThe study aimed to systematically assess community-level risk perceptions and informal resilience capacities concerning urban fluvial hazards within Peshawar, Pakistan. The research addresses the global acceleration of urban flood hazards, a phenomenon increased by unregulated urban expansion and anthropogenic climate change. Methodologically, the study adopted a qualitative inquiry and the study was framed in an Interpretive Phenomenological Approach, utilizing the Socio-Ecological Systems (SES) framework as its theoretical construct. The SES framework operationalizes the local context by integrating the core components of risk (hazard, vulnerability, and exposure) and resilience (defined by anticipatory, adaptive, and restorative capacities) within the paradigm of the human-environment relationship. Data collection employed a multi-modal strategy including nine Focus Group Discussions (FGDs), 15 Key Informant Interviews (KIIs), and five In-Depth Interviews (IDIs), all conducted via purposive sampling. The empirical data reveal that local conceptualizations of urban flooding are primarily attributed to shifts in precipitation regimes and a spectrum of anthropogenic interventions. These interventions include uncontrolled informal settlements (encroachment), faulty urbanization, elevated groundwater tables and deficiencies in critical infrastructure, with all factors being aggravated by pervasive governance deficits. The resultant vulnerability is characterized as multidimensional vulnerabilities extending across socio-economic, physical, environmental and motivational axes. Parallel to it, communities demonstrate emergent resilience mechanisms, specifically manifesting as self-organized early warning systems and adaptive structural modifications such as elevated building plinths. The study suggests that effective urban flood risk management necessitates a paradigm shift from the silos-based top-down governance model toward a holistic, risk-informed urban planning framework. Such transition requires support from institutional reforms and formalized community engagement to effectively use indigenous knowledge and local capacities, thereby adding the system’s inherent capacity to absorb, adapt and transform in response to hydrometeorological stressors.</p
Versatile HIV Rev-dependent reporter cell system for stringent and sensitive quantification of viral reservoirs, neutralizing antibodies, and restriction factors
Get PDFDetecting and measuring HIV reservoirs, neutralizing antibodies, and restriction factors are important for HIV cure research and the development of new therapeutics and vaccines. Here we describe the development and validation of several HIV Rev-dependent indicator cell lines for these purposes. These reporter cells derive from different T-lymphoblast cell lines, including Molt4-CCR5, SupT1-CCR5, CEM-SS, A3R5, and from the adherent TZM cell platform based on HeLa clone JC53. These cells express CD4, CXCR4, and various levels of CCR5. We compared these cell lines for responsiveness to both X4 and R5-tropic viruses, and confirmed that reporter expression in these cells is not affected by stimulation from mitogens but is responsive to HIV Tat and Rev, reducing non-specific reporter induction from the leaky LTR promoter. To validate the sensitivity of the Rev-dependent reporter cell systems, we conducted a viral dilution assay with three primary HIV-1 clade C swarms from an adult in Malawi. We also validated the systems for quantifying antibody neutralization and screening restriction factors; these systems are also sensitive for viral outgrowth assays for quantifying viral reservoirs in clinical and basic research settings. Given that the systems can measure HIV accurately in complex environments with mitogens or other substances, they can be used for versatile applications, such as quantifying latent reservoirs, testing inhibitory compounds, conducting neutralizing antibody assays, and identifying new restriction factors.</p
Timing of Screening Benefit for Lung Cancer With Low-Dose CT Imaging
No full textBackgroundIncreasing evidence supports lung cancer screening with low-dose CT (LDCT) imaging. However, the benefits of LDCT screening for lung cancer may not be immediate, making it unlikely to benefit patients with limited life expectancy.Research QuestionWhat is the time to benefit (TTB) from LDCT screening for individuals at high risk for lung cancer
Using Model-Based Geostatistics to Refine Population-Based Estimates of Trachoma Prevalence: Update from a Technical Consultation
Get PDFTo explore how model-based geostatistics (MBG) could support trachoma elimination efforts, a technical consultation was held on March 4 and 5, 2024 by the Centre for Health Informatics, Computing, and Statistics at Lancaster University, United Kingdom, a WHO Collaborating Centre on Geostatistical Methods for Neglected Tropical Disease Research. The meeting aimed to foster collaboration for sharing insights on using MBG for decision-making; showcase its applications in assessing trachoma elimination status; address challenges, such as setting the probability threshold for elimination and resolving conflicts between survey and MBG evidence; and discuss considerations for integrating MBG into Tropical Data. Participants, including trachoma program managers, experts, academics, donors, and statisticians, reviewed MBG applications, discussed ongoing studies, identified knowledge gaps, and planned future work. This article summarizes the meeting's presentations, discussions, and outcomes, highlighting current conclusions on and research priorities to evaluate MBG's feasibility and utility in trachoma elimination programs.</p
Early antiplatelet treatment for minor stroke following thrombolysis: the EAST trial
Get PDFBackground and AimsAntiplatelet treatment is recommended to start 24 h after intravenous thrombolysis due to concerns about haemorrhagic transformation. This study aimed to investigate the potential benefit of early antiplatelet after intravenous thrombolysis in minor stroke.MethodsA multicentre, double-blind, randomized trial was conducted in China between 7 August 2022 and 1 August 2024, to evaluate the efficacy and safety of early antiplatelet in acute ischaemic stroke patients presenting with mild neurological deficits, as indicated by a National Institutes of Health Stroke Scale (NIHSS) score of 0–5, who received intravenous thrombolysis. Patients were randomly assigned to receive either clopidogrel and aspirin or placebo within 6 h after intravenous thrombolysis. The primary endpoint was an excellent functional outcome at 90 days, indicated by a modified Rankin Scale (mRS) score of 0–1. Statistical analysis was based on a modified intention-to-treat population. Symptomatic intracranial haemorrhage, any intracranial haemorrhage, and major systemic bleeding were safety endpoints.ResultsThe primary endpoint was not met in this study. Of the randomly assigned 1022 patients, 995 patients were included in the modified intention-to-treat analysis (503 with early antiplatelet treatment and 492 with placebo). The primary endpoint occurred in 89.7% (451/503) of patients receiving early antiplatelet vs 89.6% (441/492) of those receiving placebo with no significant difference (odds ratio 1.00, 95% confidence interval .67–1.51, P = .99). Similar safety profiles were found between the two groups.ConclusionsAmong Chinese patients with acute minor ischaemic stroke who received intravenous thrombolysis, early antiplatelet treatment with clopidogrel plus aspirin was safe but did not improve already excellent functional outcome (mRS 0–1) at 90 days
Dynamic interactions between Schistosoma haematobium, Schistosoma mattheei and Schistosoma mansoni underscore the complex polyparasitism of intestinal schistosomiasis in southern Malawi
Get PDFSchistosomiasis is prevalent among school-aged children (SAC) in Mangochi District, Malawi, where both intestinal and urogenital forms are endemic. In 2024, we identified schistosomiasis cases predominantly associated with excretion of Schistosoma haematobium × Schistosoma mattheei ova in the faeces of two individuals from Samama village, Mangochi District. In this expanded cross-sectional study, we characterize the prevalence and species composition of Schistosoma infections among 247 SAC in Samama, using genus- and species-specific molecular diagnostics. We also present follow-up data from the two previous cases, showing natural mixed-species re-infection six months after treatment. Schistosomiasis prevalence among SAC was 62.3%. Schistosoma spp. DNA was detected in 50.6% of faecal samples and Schistosoma spp. ova were observed on 34.8% of urine filters. Species-specific assays detected S. haematobium, S. mattheei and S. mansoni DNA in 36.8%, 14.4% and 18.4% of faecal samples from children with intestinal schistosomiasis. Triple-species infections were identified in 10 children by faecal and urine testing. Notably, detection of S. haematobium DNA in faeces was strongly associated with S. mattheei co-infection (p = 0.006), highlighting potential cross-species interactions. Our findings underscore the need to integrate molecular diagnostics alongside routine testing strategies for enhanced surveillance of polyparasitic infections in zoonotic transmission zones across Africa. This article is part of the Royal Society Science+ meeting issue 'Parasite evolution and impact in action: exploring the importance and control of hybrid schistosomes in Africa and beyond'.</p
Rehabilitation for individuals with post-tuberculosis lung disease
Get PDFTuberculosis (TB) continues to be a global clinical and public health threat, particularly in low- and middle-income countries. TB care has primarily been centred around timely diagnosis and expanding access to treatment. Post-TB lung disease (PTLD), characterised by persistent respiratory symptoms, functional impairment and structural lung changes, is highly prevalent among TB survivors, with a prevalence ranging from 40% to 90%. This requires an effort to evaluate TB survivors in need of further care at the end of anti-TB treatment, for consideration of pulmonary rehabilitation.This review provides an overview of the current evidence and best practices in pulmonary rehabilitation for PTLD. This article aims to bridge the gap between evidence and practice, supporting tailored, multidisciplinary approaches to pulmonary rehabilitation, building on the existing experiences and challenges from diverse settings. Furthermore, this review supports the ongoing educational efforts of healthcare professionals to reframe TB care, placing long-term health and patient wellbeing at the centre of post-TB management
Controlled human infection with Mycobacterium tuberculosis:practical considerations for clinical trials
Get PDFControlled human infection models (CHIMs) can accelerate vaccine development for infectious diseases. Mycobacterium tuberculosis is a human-adapted pathogen that is the leading infectious cause of death worldwide. M tuberculosis infection results in a spectrum of clinical outcomes that are incompletely modelled in animals. To date, the risks of infection, prolonged treatment, and sequelae related to CHIMs with M tuberculosis have been considered ethically unacceptable. However, recent advances in bacterial engineering have resulted in safe strains that could permit M tuberculosis CHIM studies with reduced risks. In this Personal View, we address the practical considerations for conducting a pulmonary M tuberculosis CHIM study. We summarise the ethical issues of M tuberculosis CHIM studies in tuberculosis-endemic and non-endemic settings; describe safety considerations, such as optimising the challenge dose and minimising risks to third parties; and outline and prioritise clinical, microbiological, immunological, and radiological endpoints that would render such a model useful for vaccine development.</p
Development and evaluation of a novel RT-qPCR assay for detection of Crimean Congo haemorrhagic fever virus using the Genedrive(R) point-of-care platform
Get PDFINTRODUCTION: Crimean-Congo haemorrhagic fever (CCHF) is a viral haemorrhagic fever classed by the World Health Organization as a priority disease due to the lack of countermeasures. A point-of-care (POC) diagnostic test for rapid detection of positive cases to expedite patient management is not currently available but urgently needed. METHODS: We have developed an RT-qPCR assay to be used with the commercially available POC Genedrive(R) PCR platform enabling viral detection in serum with minimal sample preparation. The sensitivity and specificity of the novel assay in the Genedrive(R) was evaluated against the RealStar(R) CCHFV RT-qPCR Kit (Altona Diagnostics, Germany). RESULTS: The sensitivity and specificity in assay V1 (sample n = 150) were 94.4 % (95 % CI, 88.2-97.9) and 97.6 % (95 % CI, 87.1-99.9). For assay (n = 55) V2 sensitivity was 92.3 % (95 % CI, 74.9-99.5) and specificity was 100 % (95 % CI, 87.7-100). CONCLUSIONS: This study supports the feasibility of diagnosing CCHF using POC RT-qPCR platforms, having the potential to reduce turnaround times, leading to improved clinical management