Abstract Background HIV/TB co-infection presents substantial public-health challenges, showing greater treatment-failure and mortality rates than tuberculosis alone. Recent advances in machine learning (ML) provide a robust means of identifying high-risk patients early in the disease course. Methods This retrospective study enrolled 359 patients co-infected with HIV and TB at a single tertiary-care hospital. We extracted clinical and immunological data. The cohort was subsequently divided into training (0%) and test (0%) subsets, and class imbalance was addressed with the Synthetic Minority Over-sampling Technique (SMOTE). Six ML classifiers—Random Forest, XGBoost, LightGBM, Support Vector Machine, Extra Trees and CatBoost—were trained after grid-search hyper-parameter tuning. Model performance was assessed with the area under the receiver-operating-characteristic curve (AUC), accuracy, recall, precision, specificity and F1-score. Multi-criteria ranking was then conducted with the Technique for Order Preference by Similarity to Ideal Solution (TOPSIS). The leading model was interpreted using SHapley Additive exPlanations (SHAP). Results Overall, 304 of 359 patients (84.7%) had favourable outcomes, whereas 55 (15.3%) had unfavourable outcomes. LightGBM achieved the best overall performance (AUC = 0.771; accuracy = 84.72%; F1 = 0.522) and was ranked first by TOPSIS. SHAP analysis highlighted age, CD4 and CD8 counts, body-mass index and occupation as key predictors. Lower BMI, pronounced immunosuppression and older age were strongly associated with unfavourable outcomes, findings that align with established clinical evidence. Conclusion A gradient-boosted model (LightGBM) combined with SHAP interpretation demonstrated reliable predictive performance in HIV/TB co-infection and highlighted clinically actionable risk factors. Incorporating this tool into routine workflows could enable healthcare providers to identify high-risk individuals earlier, allocate resources more efficiently and, ultimately, improve TB-treatment success. Clinical trial registration Not applicable.
Justine Daudi Maganira, Noel Mark Makwinya, Beda John Mwang'onde
Porcine cysticercosis, caused by the larval stage of Taenia species, poses significant health and economic challenges in low and lower-middle-income regions. This study assessed the seroprevalence and risk factors associated with the transmission of porcine cysticercosis in Mpwapwa District, eastern-central Tanzania, using a commercial antigen enzyme linked immunosorbent assay (Ag- ELISA). A cross-sectional survey was conducted in Gulwe, Ving'hawe, and Igovu villages during the dry season in June 2024. Blood samples were collected from 159 household pigs, and structured questionnaires were administered to heads or representatives of 51 pig-keeping households to identify potential risk factors. Serum samples from 29 pigs tested positive for porcine cysticercosis in the Ag-ELISA assay with an apparent prevalence of 18.24 % (95 % CI: 12.57 %–25.13 %), and estimated true prevalence of 17.91 % (95 % CI: 12.66 %–24.67 %). The apparent prevalence of porcine cysticercosis varied across the villages with Gulwe showing the highest prevalence (22.58 %; 95 % CI: 12.93 %–34.79 %), followed by Ving'hawe (21.21 % 95 % CI: 8.98 %–38.91 %), and Igovu (12.50 %; 95 % CI: 5.55 %–23.15 %). Female pigs exhibited a relatively higher seropositivity rate (13.84 %; 95 % CI: 8.88 %–20.20 %) compared to male pigs (4.40 %; 95 % CI: 1.79 %–8.86 %) although this difference was not statistically significant (χ2 = 0.629, p-value = 0.428). DNA extracted from cysticerci isolated from infected pigs slaughter in the study villages was confirmed via gel electrophoresis to belong to Taenia solium. Seropositivity was higher in adult pigs (14.47 %; 95 % CI: 9.84 %–20.77 %) than in growers (3.77 %; 95 % CI: 1.74 %–7.99 %), but this difference was not statistically significant (χ2 = 0.385, p = value = 0.535). Risk factor analysis identified the pig management system (OR = 2.47, p = 0.005), household pig herd size (OR = 3.08, p = 0.003), pig pen design (OR = 2.49, p = 0.002), feed source (OR = 3.08, p = 0.000), ignorance of porcine cysticercosis (OR = 1.57, p = 0.031) and presence of open-field defecation (OR = 1.47, p = 0.025) as significant contributors to the transmission of porcine cysticercosis. This study identifies a significant burden of porcine cysticercosis in Mpwapwa District, highlighting the need for effective control strategies to combat this zoonotic disease, protect smallholder livelihoods, and align with the WHO's 2030 targets for intensified T. solium control.
Adama Ouedraogo, Patrice Ngangue, David Jean Simon
et al.
Objective This study estimated the proportion of children aged 12–23 months who were fully vaccinated in sub-Saharan Africa (SSA), explored geographical disparities across subregions and countries, and identified country-level factors associated with full vaccination (FV).Design Cross-sectional study.Setting SSA.Participants Children aged 12–23 months.Primary outcome FV.Methods Data for this study were extracted from the most recent Demographic and Health Survey (DHS) conducted in 34 SSA countries between 2012 and 2023. The study included a total weighted sample of 69 218 children. Univariate analyses were performed to describe the socio-demographic profile of the participants and estimate the proportion of FV and the proportion for each of the eight vaccines (BCG, DTP1, DTP2, DPT3, Polio1, Polio2, Polio3, Measles1) at regional level. Bivariate and spatial analyses were produced to examine existing disparities at regional, subregional and countries’ income levels. A multivariate logistic regression analysis was fitted for identifying country-level factors associated with FV.Results 54.1% (95% CI 53.7% to 54.5%) children aged 12–23 months in SSA were fully vaccinated. In addition, substantial inequalities emerged in FV coverage across countries ranging from 23.9% in Guinea to a high of 95.5% in Rwanda. The same pattern was observed for the eight vaccines. Findings also showed that children of birth order 3 and above, who were delivered at home, had received less than four antenatal visits, from poor households and households with more than 5 members, whose mothers were under 25, had primary education level and below, and had no income-generating activities were less likely to be fully vaccinated.Conclusion To achieve WHO’s global vaccination coverage target of 90% by 2030 in SSA, vaccination programmes must take account of regional, subregional and national inequities. Our findings also underline the need for interventions tailored to each SSA country’s socio-cultural context.Ethical consideration Ethical approval was not required as this is a secondary analysis of publicly available data.
Medicine (General), Infectious and parasitic diseases
Infection remains one of the greatest killers of children in the world. A large proportion of these deaths are due to infectious agents for which effective vaccines are already available.Vaccination has been one the most successful and cost-effective public health interventions of the 20th century. Data indicates that the greatest return on investment from vaccination disproportionately accrues to the poorest communities. Unfortunately, access to vaccines is not equitable, with the most vulnerable least likely to receive them.Using global data on the burden of disease, vaccination coverage, historical patterns of vaccine introduction and uptake, as well as access to currently available antigens, the talk will highlight the inequities in immunization practices and explore their causes. In addition, the talk will challenge the ethical framework that perpetuates these iniquities and suggests potential opportunities for addressing them.
Abstract Background West Nile virus (WNV) is a rapidly spreading mosquito-borne virus accounted for neuroinvasive diseases. An insight into WNV-host factors interaction is necessary for development of therapeutic approaches against WNV infection. CD11b has key biological functions and been identified as a therapeutic target for several human diseases. The purpose of this study was to determine whether CD11b was implicated in WNV infection. Methods SH-SY5Y cells with and without MEK1/2 inhibitor U0126 or AKT inhibitor MK-2206 treatment were infected with WNV. CD11b mRNA levels were assessed by real-time PCR. WNV replication and expression of stress (ATF6 and CHOP), pro-inflammatory (TNF-α), and antiviral (IFN-α, IFN-β, and IFN-γ) factors were evaluated in WNV-infected SH-SY5Y cells with CD11b siRNA transfection. Cell viability was determined by MTS assay. Results CD11b mRNA expression was remarkably up-regulated by WNV in a time-dependent manner. U0126 but not MK-2206 treatment reduced the CD11b induction by WNV. CD11b knockdown significantly decreased WNV replication and protected the infected cells. CD11b knockdown markedly increased TNF-α, IFN-α, IFN-β, and IFN-γ mRNA expression induced by WNV. ATF6 mRNA expression was reduced upon CD11b knockdown following WNV infection. Conclusion These results demonstrate that CD11b is involved in maintaining WNV replication and modulating inflammatory as well as antiviral immune response, highlighting the potential of CD11b as a target for therapeutics for WNV infection.
Wedad M. Abdelraheem, Doaa Elzaeem Ismail, Safaa S. Hammad
Abstract Background Resistance to carbapenem, the last line of treatment for gram-negative bacterial infections has been increasing globally and becoming a public health threat. Since integrons may aid in the transmission of resistance genes, the purpose of this study was to detect the frequency of class 1, 2, and 3 integrons as well as carbapenem-resistant genes in clinical isolates of P. aeruginosa that are resistant to carbapenem. Methods This study was carried out on 97 clinical isolates of P. aeruginosa isolated from wound and urine samples. The antimicrobial susceptibility for all isolates was tested by the disc diffusion method. The presence of integrons and carbapenem-resistant genes among carbapenem-resistant P. aeruginosa isolates was evaluated by conventional PCR. Results The antimicrobial resistance rate among P. aeruginosa clinical isolates was high, with imipenem resistance in 58.8% of the studied isolates. In this study, 86% of the carbapenem-resistant P. aeruginosa isolates carry carbapenemase genes, with bla VIM being the most common gene followed by the bla OXA−48 gene. Class 1 and class 2 integrons were reported in 37 (64.9%) and 10 (17.5%) of the tested carbapenem-resistant P. aeruginosa isolates, respectively. Conclusion Our data reported a high prevalence of class 1 integrons in carbapenem-resistant P. aeruginosa clinical isolates, suggesting the important role of integrons in carbapenem-resistant gene transfer among such isolates.
Irvane E. Nelson, Kobi A. Baker, Ary Faraji
et al.
Abstract Background Sugar alcohols, such as erythritol, are low-impact candidates for attractive toxic sugar baits (ATSB) to kill mosquitoes. To determine whether erythritol has a viable future in ATSB formulations, a suite of assays was conducted to diagnose toxicity mechanisms and starvation effects on mortality in Aedes aegypti (L.) as a model system. Methods We measured general carbohydrate load, glucosidase levels, and free glucose in intoxicated adult mosquitoes to observe whether sugar digestion was impaired. We assayed the effects of sugar combinations with erythritol on larvae and adults. To measure erythritol effects when mosquitoes were not resource-deprived, additional assays manipulated the prior starvation status. Results Up to 50,000 ppm of erythritol in water had no effect on larvae within 72 h, but an ammonia spike indicated diuresis in larvae as early as 4 h (F 8,44 = 22.50, P < 0.0001) after sucrose/erythritol combinations were added. Adult consumption of erythritol was diuretic regardless of the sugar pairing, while sucrose and erythritol together generated above 80% mortality (F 2,273 = 33.30, P < 0.0001) alongside triple the normal excretion (F 5,78 = 26.80, P < 0.0004). Glucose and fructose paired individually with erythritol had less mortality, but still double the fecal excretion. When ingesting erythritol-laced meals, less sugar was detected in mosquitoes as compared to after sucrose meals (χ 2 = 12.54, df = 1, P = 0.0004). Conclusions Data showed that erythritol is a linear competitive inhibitor of α-glucosidase, marking it as a novel class of insecticide in the current research climate. However, the efficacy on larvae was null and not persistent in adult mosquitoes when compared across various starvation levels. Despite significant diuresis, the combined effects from erythritol are not acute enough for vector control programs considering ATSB against mosquitoes. Graphical Abstract
Lusine Paronyan, Lilit Babayan, Haykuhi Vardanyan
et al.
Abstract Background Armenia is considered particularly vulnerable to life-threatening vector-borne diseases (VBDs) including malaria, West Nile virus disease and leishmaniasis. However, information relevant for the control of the vectors of these diseases, such as their insecticide resistance profile, is scarce. The present study was conducted to provide the first evidence on insecticide resistance mechanisms circulating in major mosquito and sand fly populations in Armenia. Methods Sampling sites were targeted based mainly on previous historical records of VBD occurrences in humans and vertebrate hosts. Initially, molecular species identification on the collected vector samples was performed. Subsequently, molecular diagnostic assays [polymerase chain reaction (PCR), Sanger sequencing, PCR-restriction fragment length polymorphism (RFLP), quantitative PCR (qPCR)] were performed to profile for major insecticide resistance mechanisms, i.e. target site insensitivity in voltage-gated sodium channel (vgsc) associated with pyrethroid resistance, acetylcholinesterase (ace-1) target site mutations linked to organophosphate (OP) and carbamate (CRB) resistance, chitin synthase (chs-1) target site mutations associated with diflubenzuron (DFB) resistance and gene amplification of carboxylesterases (CCEs) associated with resistance to the OP temephos. Results Anopheles mosquitoes were principally represented by Anopheles sacharovi, a well-known malaria vector in Armenia, which showed no signs of resistance mechanisms. Contrarily, the knockdown resistance (kdr) mutations V1016G and L1014F/C in the vgsc gene were detected in the arboviral mosquito vectors Aedes albopictus and Culex pipiens, respectively. The kdr mutation L1014S was also detected in the sand fly, vectors of leishmaniasis, Phlebotomus papatasi and P. tobbi, whereas no mutations were found in the remaining collected sand fly species, P. sergenti, P. perfiliewi and P. caucasicus. Conclusions This is the first study to report on molecular mechanisms of insecticide resistance circulating in major mosquito and sand fly disease vectors in Armenia and highlights the need for the establishment of systematic resistance monitoring practices for the implementation of evidence-based control applications. Graphical Abstract
Michael B. Bonsall, Chris Huntingford, Thomas Rawson
et al.
BackgroundBy March 2023, the COVID-19 illness had caused over 6.8 million deaths globally. Countries restricted disease spread through non-pharmaceutical interventions (NPIs; e.g. social distancing). More severe “lockdowns” were also required to manage disease spread. Although lockdowns effectively reduce virus transmission, they substantially disrupt economies and individual well-being. Fortunately, the availability of vaccines provides alternative approaches to manage disease spread. Yet, vaccination programs take several months to implement fully, require further time for individuals to develop immunity following inoculation, may not have complete coverage and/or may be imperfectly efficacious against the virus. Given these aspects of a vaccination programme, it is important to understand how NPIs (such as lockdowns) can be used in conjunction with vaccination to achieve public health goals.MethodsWe use mathematical methods to, investigate optimal approaches for vaccination under varying lockdown lengths and/or severities to prevent COVID-19-related deaths exceeding critical thresholds.ResultsWe find that increases in vaccination rate cause a disproportionate decrease in the length and severity lockdowns to keep mortality levels below a critical threshold. With vaccination, severe lockdowns can further reduce infections by up to 89%. Notably, we include simple demographics, modelling three groups: vulnerable, front-line workers, and non-vulnerable. We investigate the sequence of vaccination. One counter-intuitive finding is that even though the vulnerable group is high risk, demographically, this is a small group and critically, per person, vaccination therefore occurs more slowly. Hence vaccinating this group first achieves limited gains in overall disease control.DiscussionImportantly, we conclude that improved disease control may be best achieved by vaccinating the non-vulnerable group coupled with longer and/or more severe NPIs.
Evgenii Filippov, Sanchit Duhan, Laura Lehman
et al.
A 33-year-old man in Baltimore, Maryland, USA, with untreated HIV infection had a 74-day course of mpox with multiorgan system involvement and unique clinical findings. In this clinical experience combining 3 novel therapeutic regimens, this patient died from severe mpox in the context of untreated HIV and advanced immunodeficiency.
Inna A. Ivanova, A. A. Trufanova, A. V. Filippenko
et al.
SARS-CoV-2 can cause a decrease in the number of lymphocytes and their functional activity. In patients with COVID-19, especially with a severe course of the disease, a decrease in the quantitative composition of the main populations of lymphocytes is recorded. These indicators do not recover for a long time after recovery. However, it is still not known how long the quantitative and qualitative changes in the composition of lymphocytes will last and whether the severity of the infection affects this process. The aim of our study was to assess the quantitative and qualitative composition of the main populations and subpopulations of lymphocytes in patients with a new coronavirus infection of varying severity. 65 patients with a new coronavirus infection were examined. The average age of the subjects was 47.314.5 years. The volunteers were divided into three groups according to the severity of the infection: asymptomatic (n = 21); moderate (n = 32); severe (n = 12). The relative and absolute number of T-lymphocytes (CD3+), T-helper cells (CD3+CD4+), cytotoxic lymphocytes (CD3+CD8+), natural killers (CD3CD16+CD56+), TNK-lymphocytes (CD3+CD16CD56+) and B-lymphocytes (CD45+CD19+) were determined. To calculate the percentage of lymphocytes, whole blood was lysed with OPTILYSE C solution (Beckman Coulter, USA) and stained with monoclonal antibodies CD3+-FITC/CD8+-ECD/CD4+-PC5/CD16+CD56+PE and CD45+-Pacific Blue/CD19+-PC5 (Beckman Coulter, USA). Cytofluorometry was performed on a flow cytofluorometer Navios (Beckman Coulter, USA). The results of our studies showed that there were no statistically significant changes in the relative and absolute number of immunocompetent cells in asymptomatic patients with a new coronavirus infection, compared with the control group. With an average severity of the disease, a decrease in the relative and absolute content of CD3+ and CD8+ lymphocytes was revealed, these indicators were restored to control values six months after recovery. In patients with severe infection, there was a decrease in the relative and absolute number of T cells and cytotoxic lymphocytes. These values remained significantly below normal for six months and returned to normal only seven to eight months after recovery. Also, the volunteers of this group were found to have a decrease in the number of natural killers and TNK cells. Thus, the data obtained by us indicate that pathological changes concerning the relative and absolute number of the main populations and subpopulations of lymphocytes in patients with COVID-19 depend on the severity of the disease. The number of T-lymphocytes, cytotoxic lymphocytes, natural killer cells, that is, populations of cells that play a crucial role in effective antiviral protection, has been reduced in those who have undergone a new coronavirus infection in moderate and severe form. This information can be useful for expanding methodological approaches to the diagnosis, treatment of a new coronavirus infection, as well as measures for the rehabilitation of those who have suffered it.
Brenda Eskenazi, David I. Levine, Stephen Rauch
et al.
Abstract Background Indoor residual spraying (IRS), the coating of interior walls of houses with insecticides, is common in malaria-endemic areas. While important in malaria control, IRS potentially exposes residents to harmful insecticides. The World Health Organization recommends steps to minimize exposure; however, no programme has focused on educating populations. Methods A dramatic presentation and song were developed by study personnel and performed by lay performers in order to spread awareness of the importance of IRS and to minimize insecticide exposure. Performances were staged at 16 sprayed villages in the Vhembe District of Limpopo, South Africa, at which 592 attendees completed short questionnaires before and after the performance about behaviors that might limit insecticide exposure. Overall indices of the attendees’ change in knowledge of precautions to take prior to and after spraying to prevent insecticide exposure were analyzed using hierarchical mixed models to assess the effect of the performance on change in participants’ knowledge. Results Approximately half of attendees lived in homes that had been sprayed for malaria and 62% were female. Over 90% thought it better to allow IRS prior to the presentation, but knowledge of proper precautions to prevent exposure was low. The proportion answering correctly about proper distance from home during spraying increased from 49.4% pre-performance to 62.0% post-performance (RR = 1.26, 95% CI = 1.13, 1.41), and the proportion reporting correctly about home re-entry interval after spraying increased from 58.5 to 91.1% (RR = 1.54, 95% CI 1.35, 1.77). Attendees improved in their knowledge about precautions to take prior to and after spraying from mean of 57.9% correct to a mean of 69.7% (β = 12.1%, 95% CI 10.9, 13.4). Specifically, increased knowledge in closing cupboards, removing food and bedding from the home, covering immoveable items with plastic, and leading animals away from the home prior to spraying were observed, as was increased knowledge in sweeping the floors, proper disposal of dead insects, and discarding dirty washrags after spraying. Conclusions A dramatic presentation and song were able to increase the attendees’ knowledge of precautions to take prior to and after spraying in order to limit their insecticide exposure resulting from IRS. This approach to community education is promising and deserves additional study.
Arctic medicine. Tropical medicine, Infectious and parasitic diseases
Background and objectives: We have developed a standardized, easy-to-use in vitro model to study single- and multiple-species oral biofilms in real time through impedance technology, which elucidates the kinetics of biofilm formation in 96-well plates, without the requirement for any further manipulation. Design and Results: Using this system, biofilms of Streptococcus mutans appear to be sugar-dependent and highly resistant to amoxicilin, an antibiotic to which this oral pathogen is highly sensitive in a planktonic state. Saliva, tongue and dental plaque samples were also used as inocula to form multiple-species biofilms. DNA isolation and Illumina sequencing of the biofilms showed that the multi-species biofilms were formed by tens or hundreds of species, had a similar composition to the original inoculum, and included fastidious microorganisms which are important for oral health and disease. As an example of the potential applications of the model, we show that oral biofilms can be inhibited by amoxicilin, but in some cases they are induced by the antibiotic, suggesting the existence of responders and non-responders to a given antibiotic. Conclusions: We therefore propose the system as a valid in vitro model to study oral biofilm dynamics, including their susceptibility to antibiotics, antiseptics or anti-adhesive compounds.
Seyoum Aklilu, Sikaala Chadwick H, Chanda Javan
et al.
<p>Abstract</p> <p>Background</p> <p>Current front line malaria vector control methods such as indoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs), rely upon the preference of many primary vectors to feed and/or rest inside human habitations where they can be targeted with domestically-applied insecticidal products. We studied the human biting behaviour of the malaria vector <it>Anopheles funestus</it> Giles and the potential malaria vector <it>Anopheles quadriannulatus</it> Theobald in Luangwa valley, south-east Zambia.</p> <p>Methods</p> <p>Mosquitoes were collected by human landing catch in blocks of houses with either combined use of deltamethrin-based IRS and LLINs or LLINs alone. Human behaviour data were collected to estimate how much exposure to mosquito bites indoors and outdoors occurred at various times of the night for LLIN users and non-users.</p> <p>Results</p> <p><it>Anopheles funestus</it> and <it>An. quadriannulatus</it> did not show preference to bite either indoors or outdoors: the proportions [95% confidence interval] caught indoors were 0.586 [0.303, 0.821] and 0.624 [0.324, 0.852], respectively. However, the overwhelming majority of both species were caught at times when most people are indoors. The proportion of mosquitoes caught at a time when most people are indoors were 0.981 [0.881, 0.997] and 0.897 [0.731, 0.965], respectively, so the proportion of human exposure to both species occuring indoors was high for individuals lacking LLINs (<it>An. funestus</it>: 0.983 and <it>An. quadriannulatus</it>: 0.970, respectively). While LLIN users were better protected, more than half of their exposure was nevertheless estimated to occur indoors (<it>An. funestus</it>: 0.570 and <it>An. quadriannulatus</it>: 0.584).</p> <p>Conclusions</p> <p>The proportion of human exposure to both <it>An. funestus</it> and <it>An. quadriannulatus</it> occuring indoors was high in the area and hence both species might be responsive to further peri-domestic measures if these mosquitoes are susceptible to insecticidal products.</p>