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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
Clinicians in low‐ and middle‐income settings need better access to point‐of‐care haemoglobin tests for identifying and managing children and pregnant women with severe anaemia
Get PDFAround one in four people around the world are affected by anaemia, with 52 million person years lived with disability due to anaemia in 2021 [1]. While anaemia is common around the world, people living in sub-Saharan Africa and south Asia are most affected, with pregnant women and children bearing the brunt [1]. Severe anaemia can be life-threatening and requires prompt diagnosis and treatment. The World Health Organization lists automated full blood counts as an essential in vitro diagnostic for use in clinical laboratories, and haemoglobinometers for use in community settings and health facilities without laboratories [2]. In particular, haemoglobin is one of six pathology and laboratory tests that the World Health Organization recommends that all pregnant women should receive [3]. Point-of-care (POC) haemoglobin tests can also be useful for urgent clinical care decisions in settings where there is access to laboratories, as they can provide results very quickly. However, access to these important diagnostic tests is limited.</p
Adjusting vector surveillance for human behaviors reveals Anopheles funestus drove a resurgence in malaria despite IRS with clothianidin in Uganda
Get PDFAfter remarkable success following the implementation of indoor residual spraying (IRS) and repeated rounds of universal distribution of insecticidal treated nets in Tororo District, eastern Uganda, a switch to clothianidin-based IRS in March 2020 was associated with a resurgence of malaria transmission. A previous study suggested Anopheles funestus may be driving the resurgence. This study was undertaken to assess the role of An. funestus in the resurgence and improve our understanding of how human-vector interaction affects malaria transmission in settings with extensive vector control. Using human landing catches and human behavioral observations, we found An. funestus infective biting, calculated from human-behavior adjusted biting rates and species-specific sporozoite rates, was 4.3 (95% Confidence Interval [CI]: 1.81 to 10.33) times higher after multiple rounds of clothianidin-based IRS when transmission was high and then dropped off markedly with a switch back to the organophosphate Actellic in March 2023. This finding was bolstered by a causal analysis showing a link between clothianidin-based IRS and 8.6 (95% CI: 2.0 to 37.0) times higher human-behavior adjusted human biting rates due to An. funestus. These findings highlight the importance of integrating monitoring of human-vector interaction and vector bionomics when introducing or evaluating changes in vector control interventions.</p
Diagnostic Accuracy of 3 Mpox Lateral Flow Assays for Antigen Detection, Democratic Republic of the Congo and United Kingdom
Get PDFThe ongoing outbreaks of mpox highlight the urgent need for a rapid and low-cost diagnostic test to accurately detect and control this emerging disease. We estimated the analytical sensitivity using viral culture of the monkeypox virus clade IIb lineage B1 and clinical diagnostic performance of 3 antigen detection rapid diagnostic tests (Ag-RDT) by using skin swab samples and upper-respiratory swab samples from mpox patients in the Democratic Republic of the Congo and the United Kingdom. The analytical limit of detection was 1.0 × 104 plaque-forming units/mL, fulfilling World Health Organization recommendations. Specificity of the 3 Ag-RDTs was 100%, but sensitivity was estimated at 0.00%-15.79% using skin samples and 0.00% using respiratory samples. None of the 3 Ag-RDTs reached the World Health Organization's target clinical sensitivity, and we do not recommend them as diagnostic or screening tools for suspected mpox cases. Accurate Ag-RDTs for mpox diagnosis remain urgently needed.</p
Immune impacts of infant whole-cell and acellular pertussis vaccination on co-administered vaccines
Get PDFObjectives: We compared the effect of a heterologous wP/aP/aP primary series (hereafter mixed wP/aP) versus a homologous aP/aP/aP primary schedule (hereafter aP-only) on antibody responses to co-administered vaccine antigens in infants and toddlers. Methods: We randomised Australian infants in a 1:1 ratio to receive either a mixed wP/aP schedule (pentavalent diphtheria-tetanus-wP-hepatitis B-Haemophilus influenzae type b; DTwP-HepB-Hib vaccine at 6 weeks old, followed by hexavalent DTaP-inactivated poliovirus vaccine (IPV)-HepB-Hib vaccine at 4 and 6 months old) or aP-only priming doses of hexavalent DTaP-IPV-HepB-Hib vaccine at the same ages. All infants received 13-valent pneumococcal conjugate vaccine (13vPCV) at 6 weeks, 4 and 12 months of age and DTaP-IPV and Hib vaccine boosters at 18 months. We assessed whether the wP/aP schedule is non-inferior to the aP-only schedule for co-administered vaccine antigens (geometric mean ratio [GMR] >2/3). Registration: ACTRN12617000065392p. Results: Between March 2018 and January 2020, 150 infants were randomised (75 per arm). Responses to all 13vPCV serotypes and Hib-PRP at 6, 7, 18, and 19 months old, as well as HBsAg at 6 and 7 months old, were non-inferior (>90% probability). Conclusion: A mixed wP/aP schedule resulted in non-inferior IgG responses to co-administered vaccine antigens compared to the standard aP-only schedule for pertussis primary immunisation.</p
Wisteria floribunda agglutinin enhances Zaire ebolavirus entry through interactions at specific N-linked glycosylation sites on the virus glycoprotein complex
Get PDFEntry of Zaire ebolavirus (EBOV) into a host cell is a complex process requiring interactions between the viral glycoproteins (GPs) and cellular factors. These entry factors are cell-specific and can include cell surface lectins and phosphatidylserine receptors. Niemann–Pick type C1 is critical to the late stage of the entry process. Entry has been demonstrated to be enhanced by interactions between the virion and surface-expressed lectins, which interact with carbohydrate moieties attached to the GP. In addition, soluble lectins, including mannose-binding lectin, can enhance entry in vitro. However, the mechanism of lectin-mediated enhancement remains to be defined. This study investigated the possibility that plant lectins, Wisteria floribunda agglutinin (WFA), soybean agglutinin (SBA) and Galanthus nivalis agglutinin (GNA), which possess different carbohydrate-binding specificities, influence EBOV entry. WFA was observed to potently enhance entry of lentiviral pseudotype viruses (PVs) expressing the GP of three Ebolavirus species [Zaire, Sudan (Sudan ebolavirus) and Reston (Reston ebolavirus)], with the greatest impact on EBOV. SBA had a modest enhancing effect on entry that was specific to EBOV, whilst GNA had no impact on the entry of any of the Ebolavirus species. None of the lectins enhanced the entry of control PVs expressing the surface proteins of other RNA viruses tested. WFA was demonstrated to bind directly with the EBOV-GP via the glycans, and mutational analysis implicated N238 as contributing to the interaction. Furthermore, enhancement was observed in both human and bat cell lines, indicating a highly conserved mechanism of action. We conclude that the binding of WFA to EBOV-GP through interactions including the glycan at N238 results in GP alterations that enhance entry, providing evidence of a mechanism for lectin-mediated virus entry enhancement. Targeting lectin-ligand interactions presents a potential strategy for restricting Ebolavirus entry.</p
Guidance for conducting and evaluating serological surveys to assess interruption of yaws transmission in the context of an eradication target
Get PDFThis document provides a summary of guidance developed for national programmes on conducting serosurveys to assess yaws transmission status, with the objective of confirming yaws seroprevalence below 1% at each of three serosurveys over a period of 3–10 years after reporting the last case of active yaws in a region. It proposes active testing of children aged 1–5 years through population-based surveys and includes recommendations on survey design, sample size determination, sampling of primary sampling units (PSUs) within an evaluation unit, sampling of households within PSUs, integration with existing public health surveys, and follow-up protocols for positive results. Geospatial analysis and sustained surveillance are recommended for accurate assessment of whether transmission interruption has been achieved.</p
Exploring the role of religious leaders in promoting positive sexual practices to reduce the prevalence of HIV/AIDS amongst young adults in Aba, Nigeria: a qualitative study
Get PDFDespite attempts to control the HIV epidemic in Nigeria, especially amongst young adults, prevalence is increasing. The aim of this study was to provide insights to strengthen the positive impact of religious leaders in preventing HIV/AIDS amongst young adults. Qualitative descriptive research was carried out. Purposive sampling was used to identify religious leaders (Christian or Muslim) and young adults (aged 20–24) who are active in their faith communities in Aba, Nigeria, chosen due to its high prevalence of HIV amongst young people. Religious leaders were recruited through publicly available contact details. Young adult participants were recruited through religious youth groups on Facebook. Online, semi-structured interviews were carried out. Findings were analysed thematically. Seven religious leaders (six male, one female) and seven young adults (five male, two female), all Christian, participated. Results found that young people may lack appropriate knowledge on HIV prevention, and that this topic is not often discussed in church. Religious leaders were seen as influential, with different platforms to engage youth. They could have a positive or negative impact on HIV prevention practices, for instance, by reinforcing stigmatising rhetoric around HIV and discouraging condom use. Capacitating religious leaders with adequate knowledge on HIV and supporting the adoption of a more liberal and pragmatic approach to HIV/AIDS prevention may enable positive impact
Time in target range of fasting blood glucose ranges defined by WHO and ADA guidelines and cardiorenal Risk:Insights from two cohorts
Get PDFAims: Through the utilization of the time in target range (TTR), our study aims to reassess the differential risks of cardiorenal diseases associated with inconsistent pre-diabetes criteria, as defined by the World Health Organization (WHO) and the American Diabetes Association (ADA). Methods: We performed a pooled analysis from the Atherosclerosis Risk in Communities study and the Multi-Ethnic Study of Atherosclerosis study. TTR for each patient was calculated using linear interpolation before the outcome. Cox regression models were used to assess the association of fasting plasma glucose (FPG) TTR with the clinical outcomes. Results: A total of 14,346 patients were included. Using adjusted Cox regression model, both ADA (HR: 1.17, 95 % CI: 1.09 to 1.25) and WHO (HR: 1.37, 95 % CI: 1.21 to 1.57) defined pre-diabetes range were associated with an increased risk of major adverse cardiovascular events (MACE). Additionally, individuals with FPG levels in the range between the two standards (100–110 mg/dL) also had a higher risk of MACE (HR: 1.24, 95 % CI: 1.09 to 1.40). Meanwhile, no significant relation was found between FPG threshold and Chronic kidney disease (CKD). Conclusions: The threshold defined by the ADA guidelines serves to protect cardiovascular health across a broader population while not increasing the risk of CKD.</p
Testing the feasibility and utility of an executive function battery for use with primary school-aged students in Malawi
Get PDFThere is increasing evidence that malaria impacts student educational outcomes, in part through impairments in cognitive function. Currently, there is no consensus with regards to standardized tools or approaches to assess the extent and magnitude of this association. We conducted a pilot study to assess the feasibility and utility of a well-established tablet-based battery of executive function (EF) tasks for primary school-aged children in Malawi. We collected data from 197 students in grades 1–4 in a rural primary school in Blantyre District, Malawi. The assessment battery (“EF Touch”), which consisted of seven EF tasks that measure inhibitory control, working memory, and cognitive flexibility, was administered using open-source, standardized tablet-based software (RTI International’s Tangerine). Assessments were conducted in Chichewa, and task performance was analyzed for accessibility and challenge across different grade levels. High completion rates were observed for all tasks, and most students completed the entire battery within one hour. Task performance varied by grade, with older students generally performing better. Two tasks had poor performance and ceiling effects and were omitted from composite scores. A composite of EF task performance was normally distributed and increased with grade level.The study demonstrates the feasibility of using a common battery of EF tablet-based assessments with students in grades 1–4 in Malawi. Given the high burden of malaria in this region and its potential impact on cognitive development, these results help to establish the feasibility and utility of direct EF assessments in future studies that focus on the impact of malaria infection on cognitive and educational outcomes