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Utilizing Large language models to select literature for meta-analysis shows workload reduction while maintaining a similar recall level as manual curation
Get PDFBackground: Large language models (LLMs) like ChatGPT showed great potential in aiding medical research. A heavy workload in filtering records is needed during the research process of evidence-based medicine, especially meta-analysis. However, few studies tried to use LLMs to help screen records in meta-analysis. Objective: In this research, we aimed to explore the possibility of incorporating multiple LLMs to facilitate the screening step based on the title and abstract of records during meta-analysis. Methods: Various LLMs were evaluated, which includes GPT-3.5, GPT-4, Deepseek-R1-Distill, Qwen-2.5, Phi-4, Llama-3.1, Gemma-2 and Claude-2. To assess our strategy, we selected three meta-analyses from the literature, together with a glioma meta-analysis embedded in the study, as additional validation. For the automatic selection of records from curated meta-analyses, a four-step strategy called LARS-GPT was developed, consisting of (1) criteria selection and single-prompt (prompt with one criterion) creation, (2) best combination identification, (3) combined-prompt (prompt with one or more criteria) creation, and (4) request sending and answer summary. Recall, workload reduction, precision, and F1 score were calculated to assess the performance of LARS-GPT. Results: A variable performance was found between different single-prompts, with a mean recall of 0.800. Based on these single-prompts, we were able to find combinations with better performance than the pre-set threshold. Finally, with a best combination of criteria identified, LARS-GPT showed a 40.1% workload reduction on average with a recall greater than 0.9. Conclusions: We show here the groundbreaking finding that automatic selection of literature for meta-analysis is possible with LLMs. We provide it here as a pipeline, LARS-GPT, which showed a great workload reduction while maintaining a pre-set recall.</p
Susceptibility of diverse sand fly species to Toscana virus
Get PDFToscana virus (TOSV) is an emerging but neglected human pathogen currently circulating around the Mediterranean basin including North Africa. Human illness ranges from asymptomatic or mild flu-like syndromes to severe neurological diseases such as meningitis or meningoencephalitis. Despite its significant impact, understanding of TOSV transmission and epidemiology remains limited. Sand flies (Diptera: Phlebotominae), specifically Phlebotomus perniciosus and Phlebotomus perfiliewi, are believed to be the primary vectors of TOSV. However, the spread of TOSV to new geographical areas and its detection in other sand fly species suggest that additional species play a role in the circulation and transmission of this virus. This study investigated the vector competence of four sand fly species - P. tobbi, P. sergenti, P. papatasi, and Sergentomyia schwetzi - for two TOSV strains: 1500590 (TOSV A lineage) and MRS20104319501 (TOSV B lineage). Sand flies were orally challenged with TOSV via bloodmeals. None of the tested species showed susceptibility to the TOSV A strain. However, for TOSV B strain, P. tobbi demonstrated a high potential as a new vector, exhibiting high infection and dissemination rates. P. sergenti also showed some susceptibility to TOSV B, with the virus dissemination observed in all infected females. These finding suggests that P. tobbi and P. sergenti are new potential vectors for TOSV B. Given that P. tobbi and P. sergenti are the primary vectors of human leishmaniases in the Balkans, Turkey and Middle East, their susceptibility to TOSV could have significant epidemiological consequences. On the other hand, P. papatasi and S. schwetzi appeared refractory to TOSV B infection. Refractoriness of P. papatasi, a highly anthropophilic species distributed from the Mediterranean to the Middle East and India, suggests that this species does not contribute to TOSV circulation.</p
Allelic variation in a cluster of epsilon glutathione S-transferase genes contributes to DDT and pyrethroid resistance in the major African malaria vector Anopheles funestus
Get PDFBackground: Insecticide resistance in malaria vectors is a serious challenge to malaria control and elimination. Elucidation of the role of detoxification genes in resistance is necessary to develop targeted strategies to reduce malaria burden. Glutathione S-transferase epsilon clusters (GSTe genes) are upregulated in DDT- and pyrethroid-resistant Anopheles funestus mosquitoes across Africa. However, except for GSTe2, the molecular mechanisms behind this upregulation remain unclear. Here, we established that overexpression and allelic variation of GSTe genes contribute to insecticide resistance in African malaria vector An. funestus s.s. Methods: Transcriptomic and genomic analyses of GSTe genes were conducted, followed by in silico structural analysis, and functional characterization of GSTe3, GSTe4 and GSTe6 using metabolic assay and transgenic expression in Drosophila flies. Results: Transcriptomic and genomic analyses reveal changes in gene expression and genetic diversity of GSTes cluster in An. funestus across Africa. Cloning of cDNAs of GSTes from different regions of Africa detected allelic variants under selection, including A17D26T158-GSTe3, L135H191A189-GSTe4 in West/Central Africa, and T169S201 E210-GSTe6 present only in West/Southern Africa. Furthermore, in silico analysis of BN-GSTe3, MWI-GSTe3, BN-GSTe4, MWI-GSTe4, CMR-GSTe6 and, BN-GSTe6 alleles revealed that allelic variations increase the binding cavity in the active site of these GSTes with stronger affinities observed towards DDT and permethrin. All recombinant GSTes significantly metabolize DDT (41–63%) and permethrin (13–25%). Additionally, BN-GSTe4 (L135H191A189-GSTe4) variant significantly metabolizes deltamethrin (28.75%), compared to the wild-type allele (15.99%; p < 0.05). Transgenic expression of the GSTes in Drosophila melanogaster flies revealed reduced DDT mortalities in flies expressing the selected alleles (39–55%; p˂0.001), compared to control group (98%). Similar resistance patterns were observed toward permethrin and deltamethrin. Conclusion: These findings established the role of GSTes in conferring cross-resistance to pyrethroids and DDT, highlighting the role of these genes in metabolic resistance in An. funestus, which complicates malaria control using the above key insecticides.</p
Machine learning model to predict sepsis in ICU patients with intracerebral hemorrhage
Get PDFPatients with intracerebral hemorrhage (ICH) are highly susceptible to sepsis. This study evaluates the efficacy of machine learning (ML) models in predicting sepsis risk in intensive care units (ICUs) patients with ICH. We conducted a retrospective analysis on ICH patients using the MIMIC-IV database, randomly dividing them into training and validation cohorts. We identified sepsis prognostic factors using Least Absolute Shrinkage and Selection Operator (LASSO) and backward stepwise logistic regression. Several machine learning algorithms were developed and assessed for predictive accuracy, with external validation performed using the eICU Collaborative Research Database (eICU-CRD). We analyzed 2,214 patients, including 1,550 in the training set, 664 in the validation set, and 513 for external validation using the eICU-CRD. The Random Forest (RF) model outperformed others, achieving Area Under the Curves (AUCs) of 0.912 in training, 0.832 in internal validation, and 0.798 in external validation. Neural Network and Logistic Regression models recorded training AUCs of 0.840 and 0.804, respectively. ML models, especially the RF model, effectively predict sepsis in ICU patients with ICH, enabling early identification and management of high-risk cases.</p
Susceptibility profile of Anopheles and target site resistance mechanism against organophosphates in Cameroon.
Get PDFEscalating pyrethroid resistance in malaria vectors jeopardizes vector control, necessitating the use of alternative insecticides such as pirimiphos-methyl (organophosphate) for indoor residual spraying (IRS). Tracking the spread of resistance and elucidating its molecular basis are essential for effective resistance management against these insecticides. This study monitored resistance to two organophosphates, malathion (MA) and pirimiphos methyl (PM), in three malaria vectors (Anopheles gambiae s.s., An. coluzzii, and An. funestus s.s.) across Cameroon and explored related resistance mechanisms. WHO tube assays revealed that An. funestus s.s. populations were fully susceptible to both organophosphates; An. coluzzii populations were either fully susceptible (North) or potentially resistant (South; 97% mortality). In contrast, the two An. gambiae s.s. populations in this study were resistant: in the rural agricultural hotspots of Mangoum (94% mortality to PM; 50% to MA) and in peri-urban cultivated location of Nkolondom, which exhibited the highest resistance to both PM (80% mortality) and MA (46% mortality), associated with recorded use of organophosphates by farmers. Genotyping the Ace-1 markers revealed a close association with susceptibility profile, as no resistance allele was observed in An. funestus s.s. and in the northern population of An. coluzzii and a very low frequency in Njombe (3%). In contrast, a higher frequency of Ace-1R was observed in An. gambiae s.s. with a significant association observed with resistance (PM: OR = 20.33, P = 0.04; MA: OR = 98.33, P = 0.0019). Furthermore, analysis of 100 Ace-1 clones showed copy number variation was linked to resistance, as resistant mosquitoes displayed higher copy numbers compared to susceptible individuals. These findings suggest that malaria control with organophosphate-based IRS is a viable alternative in Cameroon; however, it will be necessary to consider the distribution of species and the development of resistance.</p
A high-resolution genomic and phenotypic analysis of resistance evolution of an Escherichia coli strain from a critically unwell patient treated with piperacillin/tazobactam
Get PDFIntroduction. Resistance to the β-lactam/β-lactamase inhibitor (BL/BLI) combination antibiotic piperacillin/tazobactam (TZP) predominantly occurs via β-lactamase enzymes, also leading to resistance to third-generation cephalosporins (3GCs). However, if β-lactamases inactive against 3GCs and inhibited by tazobactam are expressed at high levels, leading to enzyme hyperproduction, the surplus enzyme escapes inhibition by tazobactam and inactivates the antibiotic piperacillin. Hypothesis/Gap statement. Understanding this mechanism is clinically relevant, as enzyme hyperproduction can emerge upon antibiotic administration, resulting in treatment failure despite initial resistance profiles supporting TZP use. Aim. Our aim was to determine whether this was a case of within-patient evolution and by what mechanism or an acquisition of a second unrelated, more resistant, strain. Methodology. Whole-genome sequencing was performed on the isolate to determine the genetic basis of resistance. We also assessed the impact of TZP exposure on the amplification of the blaTEM-1 gene and monitored the stability of gene copy number over 5 days in the absence of antibiotic pressure. In addition, we determined the MICs of ceftriaxone and TZP, with TZP MIC contextualized in relation to gene copy number and resistance levels. Results. We report the identification of an Escherichia coli isolate that developed resistance to TZP during patient treatment but maintained sensitivity to ceftriaxone. We show that TZP resistance evolved via IS26-mediated duplication of a blaTEM-1 containing transposable unit on a plasmid, resulting in hyperproduction of TEM-1 β-lactamase, and that ten copies of blaTEM-1 induce resistance greater than 32 times the MIC. Furthermore, under experimental conditions, exposure to TZP further increases amplification of blaTEM-1, whereas, in the absence of TZP, gene copy number of IS26 and blaTEM-1 remains stable over 5 days, despite a 48,205 bp genome size increase compared to the pre-amplification isolate. We additionally detect phenotypic changes that might indicate host adaptation potentially linked to the additional genes that are amplified. Conclusion. Our analysis advances the understanding of infections caused by isolates evolving β-lactamase hyperproduction, which represents a complex problem in both detection and treatment. As 40% of antibiotics active against WHO priority pathogens in the pre-clinical pipeline are BL/BLI combinations, further investigations are of urgent concern.</p
Adherence to Perinatal Asphyxia or Sepsis Management Guidelines in Low- and Middle-Income Countries
Get PDFImportance: Most of the 2.3 million annual neonatal deaths occur in sub-Saharan Africa and South Asia, with perinatal asphyxia and neonatal sepsis being the leading causes of neonatal mortality. Most neonatal deaths are considered preventable through high-quality clinical care, which includes adherence to clinical care guidelines. Objective: To assess adherence to World Health Organization clinical care guidelines for management of perinatal asphyxia and neonatal sepsis and to identify patient-level factors in adherence among neonates who died from these conditions. Design, Setting, and Participants: This cross-sectional study obtained data from December 2015 through October 2023 from the Child Health and Mortality Prevention Surveillance (CHAMPS) catchment areas in 7 low- and middle-income countries in sub-Saharan Africa (Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa) and South Asia (Bangladesh). Participants were neonates who were born alive and were aged 0 to 28 days at the time of death and had either perinatal asphyxia or neonatal sepsis. Exposure: Medical records of neonates who died from perinatal asphyxia or neonatal sepsis determined by postmortem diagnostics. Main Outcomes and Measures: The main outcome was the proportion of deceased neonates who received guideline-adherent treatments before they died. Mixed-effect multivariable logistic regression analyses were performed to identify factors associated with administration of at least bag-valve-mask (BVM) ventilation for perinatal asphyxia. Results: Of the 1194 neonates (median [IQR] age at the time of death, 2 [1-6] days; 692 males [58.0%]) who died and were enrolled in CHAMPS with available clinical data, 476 (39.9%) died from perinatal asphyxia, 562 (47.0%) died from neonatal sepsis, and 156 (13.1%) from both conditions. These neonates had a median (IQR) birth weight of 2130 (1266-2988) g. For cases with perinatal asphyxia, guideline adherence ranged from 12.2% (n = 77) for adrenaline administration to 85.4% (540) for supplemental oxygen administration. Only 4.4% of neonates (28) with perinatal asphyxia received all recommended treatments. Among cases with neonatal sepsis, antibiotics were administered to 86.8% (623), although the recommended treatment was administered to only 61.0% (438). In multivariable analyses, neonates in whom clinicians accurately identified perinatal asphyxia were more likely to receive BVM ventilation than those who had received discordant antemortem and postmortem diagnoses (adjusted odds ratio, 2.00; 95% CI, 1.29-3.12). Conclusions and Relevance: In this cross-sectional study, clinical care guideline adherence was suboptimal among neonates who died from perinatal asphyxia or neonatal sepsis. This finding underscores the critical need to increase adherence in regions with high rates of neonatal mortality and may inform strategies for strengthening health systems to support compliance with clinical care guidelines.</p
Developing and evaluating a community-driven intervention to promote uptake of HIV and contraception services among students enrolled in colleges and universities in Zimbabwe
Get PDFIntroductionThere is a growing appreciation that community-led interventions are key to sustaining the HIV response and achieving HIV prevention and treatment targets. Together with young people in colleges/universities and Ministry of Health (MOH), we developed and evaluated a student-led intervention for promoting the uptake of HIV self-testing (HIVST), post-exposure prophylaxis (PEP) and emergency contraception (EC) among college/university students.MethodsOver 3 months, in biweekly study team meetings, two workshops with students, two meetings with MOH, and a joint workshop with students, MOH and relevant stakeholders, we co-developed an intervention for peer-led promotion/distribution of HIVST, PEP, EC and condoms. The agreed intervention was piloted in three Zimbabwean colleges/universities from December 2023 to February 2024. Student peers distributed HIVST and condoms directly, and vouchers for PEP and EC that were redeemed at college/nearby clinics. During co-development, students strongly preferred peer distribution of all commodities but this was restricted by regulatory requirements for PEP and EC. Peer distributors (n = 14) kept daily audio diaries of their experiences. In-depth interviews were held with students (n = 18), peer distributors (n = 11) and key informants (n = 12) to explore views/preferences, with participant observations and four focus group discussions to provide additional insights. We determined the intervention development and implementation costs.ResultsPeer-led distribution of HIVST, PEP and EC to college/university students was acceptable, feasible, appropriate and generally implemented as intended. PEP and EC acceptability was driven by high HIV and pregnancy risk among students, who had no easy access to services. Of 100 PEP and 257 EC vouchers distributed, 30% and 40% were redeemed, respectively. The main barrier to PEP and EC uptake was moral judgement against premarital sex, which affected female students more. Judgemental health worker attitudes also limited uptake of PEP and EC. EC voucher redemption among female students was lower versus males, aOR = 0.4 (95% CI = 0.2−0.8), p = 0.019. Redemption was also higher at the college where the nearby clinic could be accessed discreetly. Total cost of the intervention per student was 7.26−$35.52).ConclusionsStudent-led distribution of HIVST, PEP and EC was feasible, acceptable and affordable. Making the intervention more community-driven according to the 2024 WHO PEP guidelines will likely achieve great impact
The influence of social networks in adoption of integrated health interventions:A qualitative study of fishermen in Malawi
Get PDFIntroduction Social networks play a vital role in influencing individual and collective health behaviors and facilitating the diffusion of health interventions. Fishing communities in sub-Saharan Africa face socio-cultural and occupational challenges such as low literacy rates and high mobility. However, their high social cohesion creates a unique social environment for spreading health interventions. We explored the role of social relationships in mediating health intervention adoption in these communities, to inform future intervention strategies. Methods We conducted an exploratory phenomenological qualitative study between September and October 2024 nested within a large community cluster randomized trial (the FISH trial) in fishing communities in Mangochi district on the southern tip of Lake Malawi. We conducted four focus group discussions (N = 47) and 16 in-depth interviews. Data were analyzed thematically using a hybrid deductive and inductive data coding approach. Results Fishermen’s social networks included fishing friendships, kin and broader community connections that facilitated knowledge exchange, resource sharing and support provision. Familiarity, trust, desire to conform to community norms and shared community ties enabled health knowledge exchange and encouraged uptake of targeted interventions for HIV and schistosomiasis, despite fishermen’s mobility. Other facilitators at individual level included perceived susceptibility and financial incentives. Occasionally, negative rumors spread through peer networks, e.g., a link between blood sample collection and malign government agenda, contributed to disengagement with health interventions. Other factors including HIV-related stigma and prohibitive traditional beliefs interacted with social networks to hinder uptake. Discussion Fishermen’s health decisions are deeply embedded within their social structures. However, other factors operating at the individual and community level were noted to be crucial catalysts of the decision-making process. This study highlights the potential of leveraging social networks in public health strategies for mobile communities so long as they account for critical individual factors that influence health service engagement.</p
Prevalence and clinical impact of severe anaemia in referral hospitals in southern Benin
Get PDFSevere anaemia is a critical public health issue worldwide, disproportionately affecting children in Africa, where approximately 40% of children aged 6 to 59 months are impacted. It leads to significant hospital and post-hospital complications. However, there is a notable lack of research on its burden and clinical impact, particularly in Benin, where existing data are outdated. This study aims to assess the prevalence and impact of severe anaemia in two areas of perennial transmission in southern Benin. We conducted a retrospective cross-sectional study at two referral hospitals in Benin, Lagune Mother and Child University Hospital Centre (CHU-MEL) and the Departmental Hospital Centre-Zou (CHD-Z). Sociodemographic, clinical and biological information were extracted from medical records of patients admitted to paediatric ward in 2023, using a standardised questionnaire. Clinical severe anaemia was defined as anaemia with decompensation requiring blood transfusion, and biological severe anaemia as haemoglobin < 5 g/dl. A total of 7152 paediatric hospital records were included in the analysis (CHU-MEL = 4388; CHD-Z = 2764). The median (IQR, range) age was 32 (13–61; 1–228) months. Severe malaria (N = 3653/7152 [51.1%]) and clinical severe anaemia (3586/7152 [50.1%]) were the most common diagnoses with four out of five children (2836/3586 [79.0%]) clinically diagnosed with severe anaemia cases had malaria. In children with severe anaemia, the risk of death decreased slightly with year of age (aOR 0.95, 95% CI 0.92–0.99, p = 0.019). In contrast, severe malnutrition increased the risk of death (aOR 1.80, 95% CI 1.33–2.43, p < 0.001) being significant risk factors. Severe anaemia is a major contributor to paediatric hospital admissions, with severe malaria being a leading cause in these regions. This study highlights the critical need for a comprehensive management strategy for severe anaemia, particularly in the youngest children. An integrated strategy of effective malaria chemoprevention, such as post-discharge malaria chemotherapy combined with targeted nutritional interventions, are essential to mitigate mortality rates in areas with high malaria transmission, where the dual burden of malaria and nutritional deficiencies exacerbates paediatric morbidity and mortality.</p