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Four-year monitoring of the malaria vector Anopheles funestus in central-west Cameroon reveals an escalation of pyrethroid resistance combined with high malaria transmission
Get PDFBackground: Insecticide resistance presents a critical obstacle to malaria vector control, necessitating ongoing surveillance to guide control strategy. Despite widespread resistance in central Africa, the temporal adaptive changes driving resistance at both phenotypic and genetic levels remain uncharacterised. This study provides a comprehensive, four-year (2020–2023) assessment of Anopheles funestus s.s. in Mibellon, Cameroon, examining sporozoite infection rates and changes in insecticide resistance relative to 2015–2018 data. Methods: Susceptibility profile, resistance intensity and cone assays were conducted following the WHO protocols. Sporozoite infection was detected in the mosquito head/thorax by TaqMan assay, confirmed by nested-PCR. Gene expression was assessed using RT-qPCR while insecticide resistance markers were genotyped using allele-specific PCR and LNA. Results: Plasmodium sporozoite infection rates ranged from 4 to 21% with the predominance of P. falciparum while P. malariae and P. ovale contributed often as mixed infections. Pyrethroid resistance significantly increased over time, with mortalities decreasing from 77.7% in 2015 to 23.2% in 2023 for permethrin and 46.6% in 2016 to just 8.5% in 2023 for deltamethrin, while full susceptibility was noted for organophosphates. Worryingly, high intensity of resistance was recorded for all pyrethroids. Partial recovery of susceptibility with PBO suggests other resistance mechanisms beside P450-based metabolic resistance. PBO-based nets yielded high efficacy which decreases slightly over time contrasting with complete loss in efficacy of pyrethroid-only nets. Monitoring the genetic markers revealed a rapid selection of G454A-CYP9K1 and 4.3 kb SV alleles, which increased considerably and reaching high frequency during the same period in which phenotypic resistance intensified. Other resistance markers (A296S-rdl and L119F-GSTe2) varied slightly in frequency while the N485I-Ace1, 6.5 kb SV, and CYP6P9a/b_R alleles were absent throughout the years. Consistent overexpression of CYP9K1 and CYP6P9a/b genes in pyrethroid-resistant mosquitoes highlights their potential role in resistance intensification. Conclusion: The high infection rate and co-circulation of three Plasmodium species coupled with intense pyrethroid resistance pose a serious menace to malaria control in this region. To address these complex challenges, current vector control strategies should prioritize the deployment of PBO-based nets and organophosphates for IRS.</p
Patient and public involvement, engagement, and participation in practice: co-production of a creative health approach and theory of change through the ReCITE consortium-building project in Liverpool
Get PDFBackgroundCo-production with public stakeholders is increasingly recognised as an important approach to ensuring health research is relevant to communities and interventions and likely to generate sustainable change. Ideally, co-production needs to be sustained throughout different stages of research and allow stakeholders ownership of the research agenda. We explore a case study of iterative co-production conducted over a nine-month period with a wide range of disparate stakeholders that transformed into a research-ready consortium able to design and obtain funding for a creative health research programme.Main bodyThe ReCITE consortium is comprised of academics, creatives, and specialists in capacity development and community engagement in Liverpool, UK. Its main focus is health equity and coming up with new ways of working to tackle entrenched, avoidable and unfair differences in health. ReCITE led a series of six workshops in 2023 to co-produce a research programme to investigate creative approaches for improving health equity. Fifty-six stakeholders from the academic, creative and arts, health, community and voluntary sectors participated across six workshops that sought broad engagement and consolidated stakeholder input to develop a research agenda and expand the consortium. Common emerging themes were: (1) understanding complexities in funding creative health; (2) investigating storytelling as a catalyst for change; (3) achieving change through collective action; (4) the role of creative advocacy to change societal and funding structures; (5) evidencing the impact of community-led creative health interventions on health equity. These formed multiple co-produced outputs, including five pillars of a theory of change for the research that underpinned the research questions and determined five interventions to take forward by the research-ready consortium to securing funding for future work.ConclusionThe iterative process of gaining stakeholder input, consolidating it, and seeking further input, helped to incorporate the perspectives of different stakeholder groups into different project outputs. Equitable power-sharing guided decision-making over what to prioritise was important in building ownership of the research agenda and trust among stakeholders. However, this was a lengthy iterative process and sustaining time commitment was difficult for those stakeholders who were not fully funded to participate
Artemether-lumefantrine versus pyronaridine-artesunate for the treatment of malaria in patients with mild to moderate COVID-19 in Kenya and Burkina Faso: a randomised open-label trial (MALCOV)
Get PDFBackground: It is unknown whether the choice of malaria treatment for uncomplicated malaria affects coronavirus disease 2019 (COVID-19) severity, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load, or duration of viral shedding. Several antimalarials exhibit antiviral activity against SARS-CoV-2 in-vitro and have been suggested as potential therapeutic candidates for COVID-19, particularly pyronaridine-artesunate (PA), despite disappointing clinical results with chloroquine and hydroxychloroquine.Methods: We conducted an open-label randomised trial comparing standard 3-day treatment with PA and artemether-lumefantrine (AL) in newly diagnosed SARS-CoV-2 infected patients aged >=6 months with rapid diagnostic test or microscopy-confirmed non-severe malaria in Kenya and Burkina Faso. SARS-CoV-2 was assessed by RT-PCR on days 3, 7, 14, and 28, and symptom resolution was assessed daily for 14 days using FLU-PRO-Plus. The primary endpoint was the proportion of participants with SARS-CoV-2 clearance by day 7. Secondary endpoints included SARS-CoV-2 clearance by days 14, 21, and 28, time to SARS-CoV-2 clearance over 28 days, median viral load on day 7, and time to symptom resolution. Complete case analysis was conducted using log-binomial regression for binary outcomes, Cox-regression for time-to-event outcomes, and negative binomial regression for count outcomes, all adjusted for disease severity and viral load at enrolment. The trial is registered with ClinicalTrials.gov NCT04695197.Findings: From January 2021 to January 2022, 143 participants were randomised (PA=69, AL=74, intention-to-treat [ITT] population), including 117 with reverse transcription polymerase chain reaction (RT-PCR) confirmed (PA=58, AL=59, modified intention-to-treat [mITT] population) and 26 with rapid-antigen test confirmed SARS-CoV-2 infection. The median age was 19 years (interquartile range [IQR] 13-38), 66% were aged >=15 years. Baseline characteristics were comparable. SARS-CoV-2 clearance by day-7 (primary endpoint) was 41% (22/54) with PA versus 58% (33/57) with AL (adjusted risk ratio [aRR]=0.78, 95% confidence interval [CI] 0.45-1.35, p=0.37); by day-14: PA=80% (44/55) versus AL=96% (55/57) AL (aRR=0.86, 0.58-1.29, p=0.47). Median (IQR) viral load on day-7 was higher with PA (855 [30-2883] versus AL:81 [12-209] copies/mL, p=0.023). Time to SARS-CoV-2 clearance over 28 days was slower with PA (adjusted hazard ratio [aHR]: 0.55, 0.37-0.83, p=0.004). Time to symptom clearance between treatments was similar (aHR=1.01, 0.91-1.13, p=0.79). Parasitological cure rates by day 42 were PA=100% and AL=99%. Five serious adverse events occurred (PA=2, AL=3) in three participants (PA=1, AL=2), including three hospitalisations (PA=1, AL=2), resulting in two deaths, both from respiratory failure (PA=1, AL=1). No serious adverse events (SAEs) were considered treatment-related. Interpretation: Pyronaridine-artesunate in COVID-19 patients co-infected with malaria was associated with slower viral clearance than standard treatment with artemether-lumefantrine but similar symptom resolution. Both treatments were highly effective as antimalarials and should continue to be considered first- or second-line treatments options for uncomplicated malaria in patients with mild to moderate COVID-19.<br/
Optimal timing of induction of labour to improve maternal and perinatal outcomes: protocol for an individual participant data and network meta-analysis
Get PDFINTRODUCTION: Despite advances in maternity care, stillbirth remains a major burden. It disproportionately affects black and Asian mothers, those with obesity and women over the age of 35 years. Induction of labour may benefit these women, but there is no clear evidence to guide recommendations on optimal timing of induction because of variations in the intervention and insufficient power in primary trials for rare outcomes such as stillbirth and perinatal mortality, or to assess whether effects differ by maternal characteristics. We will conduct an individual participant data (IPD) meta-analysis of randomised trials to assess the overall and differential effect of induction of labour, according to timing of induction and maternal characteristics, on adverse perinatal and maternal outcomes. We will also rank induction of labour timing strategies by their effectiveness to inform clinical and policy decision-making. METHODS AND ANALYSIS: We will identify randomised trials on induction of labour by searching MEDLINE, CINAHL, EMBASE, BIOSIS, LILACS, Pascal, SCI, CDSR, ClinicalTrials.gov, ICTRP, ISRCTN registry, CENTRAL, DARE and Health Technology Assessment Database, without language restrictions, from inception to June 2025. Primary researchers of identified trials will be invited to join the OPTIMAL Collaboration and share the original trial data. Data integrity and trustworthiness assessment will be performed on all eligible trials. We will check each study's IPD for consistency with the original authors before standardising and harmonising the data. Study quality of included trials will be assessed by the Cochrane Risk of Bias tool. We will perform a series of one-and-two-stage random-effects meta-analyses to obtain the summary intervention effect on composite adverse perinatal outcome (stillbirth, neonatal death or severe morbidity requiring admission to neonatal unit) with 95% CIs and summary treatment-covariate interactions (maternal age, ethnicity, parity, socioeconomic status, body mass index and method of conception). Heterogeneity will be summarised using tau2, I2 and 95% prediction intervals for effect in a new study. Sensitivity analysis to explore robustness of statistical and clinical assumptions will be carried out. Small study effects (potential publication bias) will be investigated using funnel plots. ETHICS AND DISSEMINATION: The study is registered on PROSPERO (CRD420251066346) and ethics approval is not required. We will disseminate findings widely to women, healthcare professionals and policymakers through academic, professional bodies and social media channels, and in peer-reviewed journals to achieve impact. PROSPERO REGISTRATION NUMBER: CRD420251066346.</p
Selectivity screening of cytotoxicity evoked by viper venoms and their toxins after nanofractionation
Get PDFCytotoxicity is a major pathological effect that can occur during snakebite envenoming. To better understand the underlying biochemical and molecular mechanisms behind snake venom-induced cytotoxicity, it is essential to use appropriate in vitro tools for bioassaying cytotoxicity evoked by snake venoms. Identifying the toxins causing cytotoxicity is also important in this regard, particularly in the context of developing more effective snakebite treatments. Cytotoxicity induced by venom toxins can result in local pathologies in snakebite victims, which can result in long-term morbidity, and is frequently observed after bites by medically important vipers. In the present study, we optimized and applied an analytical cytotoxicity profiling platform for in vitro cytotoxicity assessment of viper venoms. Using four cell lines (RPTEC/TERT1, HepaRG, iPSC-EC, HaCat), we applied an imaging analysis assay together with resazurin reduction to identify the mechanisms of cytotoxicity at the level of cell necrosis, extracellular matrix (ECM) degradation and/or cell apoptosis. Strong cytotoxic peaks are consistent with ECM-associated cytotoxic effects, as reflected by pronounced reductions in cell area and monolayer integrity. These cytotoxicity bioassays were integrated into nanofractionation analytics and high throughput venomics, which allowed for the identification of viper venom cytotoxins at the biological and chemical levels. Venom profiling showed ECM degradation as the main cytotoxic mechanism, except for Daboia russelii, which induced necrosis and apoptosis in three cell lines. Cytotoxicity largely disappeared after reversed-phase separation, prompting use of non-denaturing SEC in nanofractionation analytics, which revealed strong cytotoxic peaks for Bothrops jararaca and Calloselasma rhodostoma in RPTEC/TERT1 cells. The methodology presented here combined analytical and biochemical tools allowing rapid cytotoxicity profiling of viper venom toxins in parallel with toxin identification.</p
Public health challenge of hybridization in urogenital schistosomiasis: New insights and one health perspectives from Malawi
Get PDFThe emergence of hybrid schistosomes resulting from interspecies mating between human and animal Schistosoma species is set to reshape the epidemiology of urogenital schistosomiasis in Malawi. Findings from the hybridization in urogenital schistosomiasis (HUGS) study in Malawi confirm the occurrence and circulation of S. haematobium × S. mattheei in humans, livestock and snails, from exemplar studies in Nsanje and Mangochi districts. Introgressed schistosomes complicate traditional diagnosis with atypical egg morphologies that defy standard microscopic identification, challenge current preventive chemotherapy strategies and raise concerns about long-term performance of mass drug administration considering zoonotic transmission inputs. With the recent completion of the multidisciplinary 4-year HUGS investigation, analysis of data reveals expanded infection risk among adults engaged in water-dependent occupations and highlights shared water bodies as key sites for human-animal-snail contact and hybrid emergence. This new One Health perspective introduces climate-driven ecological shifts, poor livestock management and lack of vector control strategies as circumstances that promote hybrid dispersal and environmental persistence. There is an urgent need to revise national schistosomiasis control strategies in Malawi, with incorporation of appropriate One Health dimensions. Looking ahead, better inclusion of hybrid schistosome surveillance into public health frameworks with intervention target indicators is needed to safeguard disease control gains and prevent future resurgence. 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
Optimal timing of induction of labour to improve maternal and perinatal outcomes: protocol for an individual participant data and network meta-analysis
Get PDFINTRODUCTION: Despite advances in maternity care, stillbirth remains a major burden. It disproportionately affects black and Asian mothers, those with obesity and women over the age of 35 years. Induction of labour may benefit these women, but there is no clear evidence to guide recommendations on optimal timing of induction because of variations in the intervention and insufficient power in primary trials for rare outcomes such as stillbirth and perinatal mortality, or to assess whether effects differ by maternal characteristics. We will conduct an individual participant data (IPD) meta-analysis of randomised trials to assess the overall and differential effect of induction of labour, according to timing of induction and maternal characteristics, on adverse perinatal and maternal outcomes. We will also rank induction of labour timing strategies by their effectiveness to inform clinical and policy decision-making. METHODS AND ANALYSIS: We will identify randomised trials on induction of labour by searching MEDLINE, CINAHL, EMBASE, BIOSIS, LILACS, Pascal, SCI, CDSR, ClinicalTrials.gov, ICTRP, ISRCTN registry, CENTRAL, DARE and Health Technology Assessment Database, without language restrictions, from inception to June 2025. Primary researchers of identified trials will be invited to join the OPTIMAL Collaboration and share the original trial data. Data integrity and trustworthiness assessment will be performed on all eligible trials. We will check each study's IPD for consistency with the original authors before standardising and harmonising the data. Study quality of included trials will be assessed by the Cochrane Risk of Bias tool. We will perform a series of one-and-two-stage random-effects meta-analyses to obtain the summary intervention effect on composite adverse perinatal outcome (stillbirth, neonatal death or severe morbidity requiring admission to neonatal unit) with 95% CIs and summary treatment-covariate interactions (maternal age, ethnicity, parity, socioeconomic status, body mass index and method of conception). Heterogeneity will be summarised using tau2, I2 and 95% prediction intervals for effect in a new study. Sensitivity analysis to explore robustness of statistical and clinical assumptions will be carried out. Small study effects (potential publication bias) will be investigated using funnel plots. ETHICS AND DISSEMINATION: The study is registered on PROSPERO (CRD420251066346) and ethics approval is not required. We will disseminate findings widely to women, healthcare professionals and policymakers through academic, professional bodies and social media channels, and in peer-reviewed journals to achieve impact. PROSPERO REGISTRATION NUMBER: CRD420251066346.</p
PANDA e-health system as a tool to increase antenatal contacts and improve perinatal outcomes in Tanzania: adaptation and feasibility study
Get PDFBackground: Antenatal attendance is critical for pregnant women to receive the screening, health education and care plans that can optimise positive perinatal outcomes. In Tanzania, few women achieve the WHO-recommended 8 contacts with health workers, partly due to the limited screening and diagnosis services offered and health workers’ disrespectful attitudes. Mobile health solutions have potential to support the provision of comprehensive and respectful antenatal consultations, but these need to be rigorously assessed. The study aimed to adapt the Pregnancy and Newborn Diagnostic Assessment e-health system (PANDA), to incorporate respectful care prompts, and assess the feasibility of the new PANDA system to deliver prenatal care to women in rural Tanzania. Methods: A prospective, pre- and post-cohort mixed-methods study over 12 months was carried out in two primary facilities and one linked referral hospital. One hundred and sixty pregnant women (1st or 2nd trimester) were recruited; 80 received usual prenatal care and 80 received care through PANDA. Feasibility outcomes comprised recruitment and retention of women into the study, acceptability of the intervention and research processes, intervention fidelity, feasibility of data collection, confirmation of trial outcome measure and quality of implementation. Results: Incorporation of respectful care prompts was achieved and considered acceptable. The study recruited to target (> 90%) in both groups and 100% of women were retained in the study. Fidelity of the PANDA package, including training, was confirmed through observations and clinical data. Two interlinked themes summarised the qualitative narratives: PANDA supports relational care, and PANDA enables systematic and personalised ANC provision. PANDA was considered a positive intervention, although its use prolonged the first consultation duration. Conclusion: Acceptability of PANDA use and feasibility of study processes were demonstrated. Participants’ and stakeholders’ feedback have informed refinement of the PANDA package and its implementation strategy ahead of commencing a cluster trial to assess effectiveness. Trial registration: The study was prospectively registered (ISRCTN34645009) on 21/10/2022.</p
Clinical presentation and management of snakebite envenoming in northern Ghana
Get PDFBACKGROUND: Snakebite envenoming is among the top five emergency health conditions in northern Ghana. Among the four genera of snake species classified to be of highest medical importance, species with haemotoxic venom are responsible for about 90% of all snakebite case presentations in the region. However, there is a dearth of clinical data on signs and symptoms of envenoming, treatment practices and health outcomes. We examined the signs and symptoms of envenoming and clinical management practices at referral hospitals in northern Ghana. METHODS: Medical records of patients reporting on account of snakebite between 2016 and 2020 at the Wa Municipal Hospital in the Upper West region and the Baptist Medical Centre in the North East region of Ghana were reviewed. Demographic characteristics, patients' clinical data and management practices were analysed and evaluated taking into consideration the national standard treatment guideline. RESULTS: A total of 2,684 records of patients reporting on account of snakebite were accessed at both health facilities over the five-year period. 91% of the patients were admitted to the ward. Swelling, severe pain and bleeding were the most common clinical signs upon presentation. A total of 1,670 (64.7%) of all the patients tested had at least one abnormal blood clotting result suggesting haemotoxicity. Antivenom was administered to 84.3% of the patients. Antibiotics were administered to 70.5% with amoxicillin with clavulanic acid, flucloxacillin and metronidazole accounting for 59.2% of all antibiotics administered. The recorded case-fatality rate was 1.9%. CONCLUSION: The annual hospital attendance rate on account of snakebite to the Wa Municipal Hospital and the Baptist Medical Centre is estimated at 55 persons per 100,000 population per year. Mortality was low, with antivenom available to most of the patients. More evidence is needed on the indication and dosing of antivenom and to improve appropriate ancillary care.</p