Liverpool School of Tropical Medicine

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    One Health insights into local transmission of zoonotic Schistosoma mattheei in southern Malawi

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    Schistosoma mattheei is a zoonotic schistosome species in central and southern Africa and is of increasing public health concern in southern Malawi. To gain insight into its local transmission, we investigated the biology of Schistosoma mattheei in southern Malawi, integrating epidemiological, environmental and genetic data within a One Health framework. Cattle, goats, humans and snails were surveyed, with DNA barcoding revealing nine mitochondrial S. mattheei haplotypes. Two haplotypes were shared across species, indicating cross-host transmission. Infected snails were detected year-round, with seasonal variation linked to vegetation cover (Normalized Difference Vegetation Index (NDVI)). Praziquantel (40 mg kg -1) treatment in selected cattle herds reduced infection prevalence over 12 weeks. These findings highlight the zoonotic potential of S. mattheei and the need for integrated control strategies. 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

    Environmental enteric dysfunction, systemic inflammation, growth hormones, and linear growth in infants in western Kenya: a prospective observational cohort study

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    Background: Environmental enteric dysfunction is associated with chronic systemic inflammation that results in growth hormone resistance and impaired growth although associations differ between settings. Objectives: We aimed to describe the time of onset and progression of intestinal pathology and explore associations between biomarkers of environmental enteric dysfunction, systemic inflammation, growth hormones, and linear growth in infants in western Kenya. Methods: In this prospective, observational cohort study, analysis is limited to infants recruited to the control arm (no intervention) of the PROSYNK trial between 28 October, 2020, and 13 January, 2022. Biomarkers of environmental enteric dysfunction, systemic inflammation, growth hormones, and infant length were measured at 6 wk and 3, 6, and 12 mo. Associations between biomarkers, growth hormones, and linear growth between time points were explored. Results: In 149 infants at age 6 wk, fecal myeloperoxidase (a biomarker of intestinal inflammation) was raised (≥0.2 mg/dL) in 47 of 143 (32.9%) and fecal α1-antitrypsin (intestinal permeability; ≥26.8 mg/dL) in 26 of 142 (18.3%) infants. Chronic systemic inflammation (plasma α1-acid glycoprotein, &gt;1 g/dL) occurred from age 3 mo (33/140 infants; 23.6%). Once detected, intestinal inflammation, increased intestinal permeability, and chronic systemic inflammation persisted in most infants. Fecal myeloperoxidase, fecal α1-antitrypsin, and plasma intestinal fatty acid–binding protein (intestinal integrity) were significantly positively associated with chronic systemic inflammation at some time points. Chronic systemic inflammation was significantly negatively associated with insulin-like growth factor 1 and insulin-like growth factor–binding protein 3 at 3, 6, and 12 mo. In multiple regression analysis, fecal α1-antitrypsin at age 6 mo was negatively associated with subsequent change in length-for-age z-score (n = 124; coefficient: −0.32; 95% CI: −0.50, −0.13; P = 0.001). Conclusions: Targeting young infants with environmental enteric dysfunction, and especially increased gut permeability, may prevent or ameliorate chronic systemic inflammation and improve growth and development in infants in western Kenya. The PROSYNK trial was registered at the Pan African Clinical Trials Registry (https://pactr.samrc.ac.za/) as PACTR202003893276712 (https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=9798).</p

    Household determinants of healthcare utilisation in three informal settlements in Freetown, Sierra Leone a cross-sectional survey

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    OBJECTIVE: Healthcare utilisation (HU) is key to improving the health of residents in urban informal settlements. This study aimed to explore household-level factors influencing HU among informal settlement households in Freetown, Sierra Leone. DESIGN: Cross-sectional survey. SETTING: Three informal settlements (Cockle Bay, Dwarzark and Moyiba) in Freetown, Sierra Leone. PARTICIPANTS: Primary data from 4871 households were collected during the Health and Wellbeing survey conducted between April and May 2023, targeting households with adults aged 18 years and older. PRIMARY OUTCOME MEASURES: The primary outcomes were households HU both within and outside informal settlements. Household-level predisposing and enabling explanatory variables were derived from Andersen's Behavioural Model of HU. RESULTS: Disability in households increases HU within settlements (especially in Dwarzark, 13% and Moyiba, 10%) but is less likely outside. Households engaged in income-generating activities are more likely to seek healthcare within settlements, but 12% less likely outside in Cockle Bay and Dwarzark. Food insecurity decreases HU within Dwarzark (9%) and increases HU outside by 174% in Moyiba. Longer water fetching times and water shortages were associated with higher HU (between 6% and 16%) within settlements, especially in Cockle Bay and Dwarzark. Clean water sources (eg, piped dwelling, bowser, surface, bottled) were consistently associated with higher HU both within and outside settlements. Shared sanitation facilities (such as shared toilets) were positively associated with HU both within and outside settlements, particularly in Dwarzark and Moyiba. Households with income from fishing, informal salaried work and bike riding showed higher HU both within and outside settlements, especially in Dwarzark and Moyiba. CONCLUSIONS: We identified strong settlement-specific patterns of household-level factors that influence HU both within and outside Freetown's informal settlements. These findings provide a foundation for developing targeted policies such as strengthening local services, addressing affordability and accessibility barriers and supporting vulnerable occupation groups.</p

    Impact of sex on outcomes in patients treated with drug-coated balloons versus drug-eluting stents for de novo coronary artery lesions: Insights from the REC-CAGEFREE I trial

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    Background: The anatomical and pathophysiological characteristics of coronary artery disease vary between the sexes. This study investigated the impact of sex on outcomes in patients with de novo coronary artery lesions treated with drug-coated balloons (DCB) or drug-eluting stents (DES). Methods: REC-CAGEFREE I was an investigator-initiated, non-inferiority trial conducted at 43 sites in China from Feb 5, 2021, to May 1, 2022, which randomized 2,272 patients for treating de novo coronary lesions, regardless of vessel diameter. After successful lesion pre-dilatation, eligible patients were randomized (1:1) to either DCB angioplasty with the option of rescue stenting or intended DES deployment. In this prespecified subgroup analysis, patients were analyzed by sex based on their medical records. The primary endpoint was device-oriented composite endpoint (DoCE), including cardiovascular death, target-vessel myocardial infarction, and clinically and physiologically indicated target lesion revascularization at 2 years. Between-group differences were compared by Cox proportional-hazards models, and imbalances in baseline characteristics were adjusted with inverse probability of treatment weighting (IPTW). The analyses were conducted in the intention-to-treat population. Results: A total of 2,272 participants underwent randomization, of which 698 (30.7%) were female and 1,574 (69.3%) were male. At 2 years, no statistically significant differences in the incidence of DoCE were observed between sexes (36 [5.2%] for females and 74 [4.7%] for males, HRIPTW:1.04, 95%CI:0.67 to 1.61, P = 0.877). Compared with DES, DCB was associated with a numerically higher risk of DoCE in females (6.3% versus 3.9%, HRIPTW:1.55, 95%CI:0.78 to 3.11, P = 0.210) and a statistically significant higher risk in males (6.4% versus 3.1%, HRIPTW:2.28, 95%CI:1.40 to 3.70, P = 0.001), respectively, with no significant sex-by-treatment (DCB/DES) interaction observed (Pinteraction = 0.575). The prognosis of DCB and DES differed significantly between small vessel disease (SVD) and non-SVD among females (Pinteraction = 0.007), but not among males (Pinteraction = 0.408). Conclusions: For patients with de novo, non-complex coronary artery disease, DCB was associated with a significantly higher risk of 2-year DoCE compared with DES in males, whereas a consistent but non-significant trend was observed in females. Trial registration: ClinicalTrials.gov identifier: NCT04561739.</p

    Establishing the Kenya National Antivenom Quality Control Laboratory Preclinical Efficacy Results of Four Antivenoms Against Venoms from the “Big Five” Snake Species in Kenya

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    Antivenom administration is currently the only therapy for snakebite envenoming. However, in sub-Saharan Africa, inadequate quality control systems have led to deficits in the availability, accessibility, efficacy and safety of regionally available antivenoms, which, in turn, hinder snakebite treatment and management in the region. To address this impediment to snakebite treatment in Kenya, this study aimed to assess the preclinical neutralising potencies of four different antivenoms previously or currently available in Kenya (SAIMR polyvalent, AFRIVEN, PANAF-PremiumTM and InoserpTM) against key snakes of medical importance in the region, towards establishing a national antivenom quality control laboratory. Venoms were extracted from the Kenyan “big five” medically important snake species: Naja ashei, Naja pallida, Naja nigricollis, Dendroaspis polylepis and Bitis arietans, and their lethal potencies were determined using a murine median lethal dose (LD50) assay. In vitro immunological assays (ELISAs and immunoblotting) and an established preclinical murine in vivo neutralisation assay (median effective dose [ED50]) were used to assess the immunoglobulin-binding and venom-neutralising efficacies of the test antivenoms. In vitro assays revealed high venom-binding titres of SAIMR polyvalent, AFRIVEN and PANAF-PremiumTM, and reactivity to a wide range of venom proteins across the different snake venoms. Contrastingly, InoserpTM antivenom had low binding titres and poor reactivity to the snake venom proteins. These findings were aligned with the in vivo results, where SAIMR polyvalent, AFRIVEN and PANAF-PremiumTM showed potent venom-neutralising efficacies against all the tested snake venoms, while InoserpTM had low potency and failed to neutralise the lethal effects of N. ashei, N. pallida and D. polylepis venoms at the manufacture-claimed doses. Based on these robust preclinical results, we conclude that SAIMR polyvalent, AFRIVEN and PANAF-PremiumTM antivenoms offer considerable potential for the treatment of envenoming by diverse medically important snakes in Kenya. The observed deficiencies with the InoserpTM product highlight the importance of (i) robust, independent preclinical antivenom efficacy testing and (ii) the value of establishing a quality control laboratory to inform local regulatory and procurement decision making.</p

    The migratory behaviour of salt marsh mosquitoes: Revisiting the evidence

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    In the early 1950s, approximately 1.5 million radiolabelled black salt marsh mosquitoes (Diptera: Culicidae, Aedes taeniorhynchus Wiedemann) were released from a point source on Sanibel Island, part of an archipelago of barrier islands and mangrove swamps off the southwest coast of Florida, during one evening in June (Provost, 1957). Carefully synchronising the timing of larval hatch in outdoor tanks filled with water from local marshlands, the research team orchestrated a mass emergence of adults and witnessed that “wisps of mosquitoes took off spontaneously in puffs”. After sunset, newly emerged Ae. taeniorhynchus adults resting on nearby surfaces gradually departed, and before dawn “the great mass of mosquitoes had gone”. In the following days, adults were recaptured using light traps distributed across the archipelago (Figure 1). Recapture rates of females marked with radiolabelled phosphorous-32 (p32) vastly outweighed those of marked males, with the latter concentrated within just a few kilometres. Marked females, however, were found up to 40 km from the release point, mostly downwind, and significant numbers made open-water crossings at least three kilometres in length shortly after release

    Environmental enteric dysfunction, systemic inflammation, growth hormones, and linear growth in infants in western Kenya: a prospective observational cohort study

    No full text
    Background: Environmental enteric dysfunction is associated with chronic systemic inflammation that results in growth hormone resistance and impaired growth although associations differ between settings. Objectives: We aimed to describe the time of onset and progression of intestinal pathology and explore associations between biomarkers of environmental enteric dysfunction, systemic inflammation, growth hormones, and linear growth in infants in western Kenya. Methods: In this prospective, observational cohort study, analysis is limited to infants recruited to the control arm (no intervention) of the PROSYNK trial between 28 October, 2020, and 13 January, 2022. Biomarkers of environmental enteric dysfunction, systemic inflammation, growth hormones, and infant length were measured at 6 wk and 3, 6, and 12 mo. Associations between biomarkers, growth hormones, and linear growth between time points were explored. Results: In 149 infants at age 6 wk, fecal myeloperoxidase (a biomarker of intestinal inflammation) was raised (≥0.2 mg/dL) in 47 of 143 (32.9%) and fecal α1-antitrypsin (intestinal permeability; ≥26.8 mg/dL) in 26 of 142 (18.3%) infants. Chronic systemic inflammation (plasma α1-acid glycoprotein, &gt;1 g/dL) occurred from age 3 mo (33/140 infants; 23.6%). Once detected, intestinal inflammation, increased intestinal permeability, and chronic systemic inflammation persisted in most infants. Fecal myeloperoxidase, fecal α1-antitrypsin, and plasma intestinal fatty acid–binding protein (intestinal integrity) were significantly positively associated with chronic systemic inflammation at some time points. Chronic systemic inflammation was significantly negatively associated with insulin-like growth factor 1 and insulin-like growth factor–binding protein 3 at 3, 6, and 12 mo. In multiple regression analysis, fecal α1-antitrypsin at age 6 mo was negatively associated with subsequent change in length-for-age z-score (n = 124; coefficient: −0.32; 95% CI: −0.50, −0.13; P = 0.001). Conclusions: Targeting young infants with environmental enteric dysfunction, and especially increased gut permeability, may prevent or ameliorate chronic systemic inflammation and improve growth and development in infants in western Kenya. The PROSYNK trial was registered at the Pan African Clinical Trials Registry (https://pactr.samrc.ac.za/) as PACTR202003893276712 (https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=9798).</p

    Mapping resilience in conflict and recovery: A systems analysis of the health sector in Ethiopia’s Tigray region (2020–2025)

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    This study explores the resilience of the health system in Tigray (Ethiopia) in the period during and following the most recent conflict (2020–2025). The aim is to gain an understanding of the dynamic ways in which the health system has responded to the crisis and early recovery, highlighting elements of its resilience, including the resilience strategies (adaptation, absorption and transformation), resilience capacities (i.e., underlying broader capacities that the health system must have in place in order to deploy specific approaches) and resilience pathways. The study is grounded in a resilience framework and adopts a systems thinking approach, drawing on data from a documentary review, key informant interviews and focus groups in Tigray. The findings illustrate the impact of the war on elements of the health system, and the resilience strategies adopted within each element to sustain some extent the health system functionality during the conflict as well as the (longer-term) health system recovery. Based on the findings, a Causal Loop Diagram is developed, which helps to identify key emerging resilience capacities (the motivation, dedication and individual coping strategies of health workers; community trust in healthcare providers; and the regional health authority’s leadership), highlighting causal, balancing or reinforcing loops and pathways between elements, and critically exploring how resilience strategies, capacities and pathways connect and interrelate, sustaining some elements of the health system, preventing collapse and potentially supporting a return to a fully functioning healthcare system. Findings provide evidence that could support the reconstruction and recovery efforts in Tigray, and might inform recovery planning in other settings post-conflict

    Medical haematology: Repositioning haematology at the centre of medicine

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    Haematology is at a crossroads, divided between haemato-oncology and the disparate disciplines collectively known as ‘non-malignant’ haematology. This latter term is a misnomer that devalues a spectrum of complex, life-threatening conditions and contributes to workforce shortages and research inequities. This article argues for the formal adoption of the term Medical Haematology to redefine this domain. We chart its central role across medicine, from guiding anticoagulation, transfusion and thrombosis care across specialties to addressing global health challenges. We highlight its pioneering contributions to molecular medicine and immunotherapy, exemplified by gene therapy for haemophilia and the repurposing of chimeric antigen receptor T cells for autoimmune disease. Finally, we present a forward-looking blueprint involving establishment of ‘Blood Teams’, revamping educational curricula and championing equity to secure the speciality's future. Embracing Medical Haematology is a strategic imperative to reflect the life-threatening nature of many conditions within the speciality, attract trainees, rebalance research priorities and firmly re-establish haematology's indispensable role at the heart of modern medical practice.</p

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