{"title":"Analytical and clinical validation of a novel MeltPlus TB-NTM/RIF platform for simultaneous detection of <i>Mycobacterium tuberculosis complex</i>, <i>Non-Tuberculous Mycobacteria</i> and rifampicin resistance.","authors":"Zhuo Wang, Yuanwu Zou, Zihan Wei, Guanghong Bai, Xiaolin Wang, Shaoyi Qu, Jie Shi, Yaping Jiang, Cuijiao Gu","doi":"10.3389/fcimb.2025.1534268","DOIUrl":"https://doi.org/10.3389/fcimb.2025.1534268","url":null,"abstract":"<p><strong>Background: </strong>Rapid and accurate diagnosis of tuberculosis, particularly rifampin (RIF)-resistant tuberculosis (RR-TB) and <i>Non-Tuberculous Mycobacteria</i> (NTM), is essential for implementing appropriate proper therapy to benefit patients and improve TB/NTM patient management.</p><p><strong>Methods: </strong>In this study, we developed a novel MeltPlus MTB-NTM/RIF platform, designed to simultaneously detect <i>Mycobacterium tuberculosis complex</i> (MTBC), NTM and RIF resistance. The platform was evaluated for its limit of detection (LOD) and specificity before clinical validation, followed by a prospective single-center study in patients with presumptive TB cases.</p><p><strong>Results: </strong>The calculated LOD for MTBC, NTM and RIF susceptibility was found to be 10.31 CFU/mL, 57.55 CFU/mL and 48.584 CFU/mL, respectively. The assay showed a sensitivity of 98.76% (95% CI: 96.41-99.74%) and a specificity of 94.42% (95% CI: 90.82-96.92%) for MTBC detection compared to the bacteriological TB standard. For NTM detection, the assay demonstrated a sensitivity of 91.98% (95% CI: 76.32-98.14%) and a specificity of 99.59% (95% CI: 98.54-99.95%). RIF resistance detection showed a sensitivity of 90.24% (95% CI:76.87-97.28%) and specificity of 95.98% (95% CI: 91.89-98.37%), with a high level of diagnostic agreement (<i>Kappa</i>: 0.8338) compared to GeneXpert. Sanger sequencing revealed that novel assay correctly classifies 98.6% of study cases as RIF resistant or susceptible, slightly higher that of GeneXpert.</p><p><strong>Discussion: </strong>These findings indicate that the novel MeltPlus MTB-NTM/RIF platform provides a rapid and accurate method for the simultaneously detecting MTBC, NTM, and RIF resistance, making it a promising tool for clinical TB/NTM diagnosis and management, further multi-center and field studies are recommended to validate its broader applicability.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1534268"},"PeriodicalIF":4.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The <i>Mycoplasma hyopneumoniae</i> protein Mhp274 elicits mucosal and systemic immune responses in mice.","authors":"Mengqi Xie, Zhongshun Huang, Yun Zhang, Yujie Gan, Huiying Li, Dan Li, Honglei Ding","doi":"10.3389/fcimb.2025.1516944","DOIUrl":"10.3389/fcimb.2025.1516944","url":null,"abstract":"<p><strong>Background: </strong><i>Mycoplasma hyopneumoniae</i> is the etiological agent of mycoplasmal pneumonia of swine (MPS). Commercial vaccines provide partial protection and do not prevent the colonization and transmission of <i>M. hyopneumoniae</i>. The bottleneck in the development of more effective vaccines for MPS is the stimulation of effective immune responses in the host. The purpose of the present study was to evaluate the immune responses of immunodominant proteins Mhp170, Mhp274 and Mhp336 in BALB/c mice.</p><p><strong>Methods: </strong>The recombinant Mhp170 (rMhp170), Mhp274 (rMhp274), and Mhp336 (rMhp336) proteins were purified from recombinant bacteria. Fifty-two six-week-old SPF female BALB/c mice were divided into five groups: a commercial inactivated vaccine-immunized group, three recombinant protein-inoculated groups, and a PBS-treated group. The physical parameters and body weights of the mice were observed during the experiment. The lung/body coefficient and macroscopic and microscopic lung lesions were evaluated. IgG and its isotypes IgG1 and IgG2a in serum and BALF and sIgA in BALF were assessed. The levels of IFN-γ, IL-4, and IL-17, in the supernatants of splenocytes and in serum were measured, and the mRNA levels of three cytokines in splenocytes were analyzed. Finally, lymphocyte proliferation after stimulation with corresponding proteins or crude extract of <i>M. hyopneumoniae</i> J strain was assessed.</p><p><strong>Results: </strong>We successfully constructed recombinant bacteria expressing rMhp170, rMhp274, and rMhp336. None of the mice from all groups presented adverse reactions and macroscopic and microscopic lung lesions. rMhp170 and rMhp274 were capable of inducing the production of IgG, IgG1 and IgG2 in serum and BALF, the secretion of IFN-γ, IL-4 and IL-17 in serum, the expression of IFN-γ, IL-4 and IL-17 mRNAs in splenocytes, and high levels of lymphocyte proliferation. Moreover, rMhp274 significantly increased sIgA in BALF. Nevertheless, rMhp336 induced only IgG, IgG1 and IgG2 production in sera; the secretion of IFN-γ and IL-4 in sera and BALF; the expression of IFN-γ and IL-4 mRNAs in the splenocyte population; and lymphocyte proliferation.</p><p><strong>Conclusion: </strong>Mhp170 and Mhp274 induced Th1/Th2/Th17 immune responses, and Mhp336 stimulated mixed Th1/Th2-type immune responses, in mice. Our data suggest that Mhp274 is a potential viable candidate for the development of a subunit vaccine for MPS.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1516944"},"PeriodicalIF":4.6,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xi Wang, Letian Liu, Wen Wang, Yang Zhang, Hui Chen, Zhangli Wang, Jianwei Li, Yue Gao, Yanqun Huang, Lijun Sun, Tong Zhang, Aixin Li
{"title":"Mortality risk prediction model in AIDS patients with pneumocystis pneumonia in China.","authors":"Xi Wang, Letian Liu, Wen Wang, Yang Zhang, Hui Chen, Zhangli Wang, Jianwei Li, Yue Gao, Yanqun Huang, Lijun Sun, Tong Zhang, Aixin Li","doi":"10.3389/fcimb.2024.1485231","DOIUrl":"10.3389/fcimb.2024.1485231","url":null,"abstract":"<p><strong>Introduction: </strong>Pneumocystis pneumonia (PCP) is a common and serious complication of HIV/AIDS, with a higher prevalence in patients not receiving antiretroviral therapy. Due to the high mortality rate of PCP, accurate prediction of its case fatality rate is very important for clinical treatment. We aimed to develop a risk model for the near-term prognosis of people with HIV/AIDS and PCP and verify its effectiveness.</p><p><strong>Methods: </strong>This single-center, retrospective observational study was conducted at Beijing Youan Hospital from January 2012 to October 2022. 972 AIDS patients with Pneumocystis pneumonia met our criteria were recruited. The patients were divided into death group and survival group according to clinical outcome during hospitalization. Data of the two groups were collected including general information and laboratory test results. 53 medical characteristics of the two groups were collected. Prediction variables were screened with Multivariate logistic regression analysis and Lasso regression model. We used ROC curve to identify the discrimination of training and testing data sets. The Shapley Additive exPlanation (SHAP) method was applied to explain the final model and the weights of features.</p><p><strong>Results: </strong>The overall mortality rate among hospitalized patients was 17.8%. We found that the best prediction effect can be obtained when ALB, PO<sub>2</sub>, TBIL, LDH, CD4<sup>+</sup> T lymphocyte counts are incorporated into the PCP risk prediction model. The model had a perfect discrimination with AUC of 0.994 and 0.947 in training and validation cohorts. The prognosis risk grade was divided into three grades: low-risk group (0-25 points with mortality of 5.9%), moderate-risk group (25-50 points with mortality of 45.1%) and high-risk group (above 50 points with mortality of 80%). There is a statistically significant difference in mortality among these three grades (χ<sup>2</sup> = 419.271, P<0.001).</p><p><strong>Conclusion: </strong>We developed and validated a model of the prognostic risk level of PCP in patients of AIDS with the results of blood tests reviewed by patients at routine visits. The model is more convenient to use, allowing clinicians to obtain a determined probability value of PCP mortality with simple calculations within the first 72 hours of the patient's admission.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"14 ","pages":"1485231"},"PeriodicalIF":4.6,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anthony Huffman, Mehul Gautam, Arya Gandhi, Priscilla Du, Lauren Austin, Kallan Roan, Jie Zheng, Yongqun He
{"title":"Systematic collection, annotation, and pattern analysis of viral vaccines in the VIOLIN vaccine knowledgebase.","authors":"Anthony Huffman, Mehul Gautam, Arya Gandhi, Priscilla Du, Lauren Austin, Kallan Roan, Jie Zheng, Yongqun He","doi":"10.3389/fcimb.2025.1509226","DOIUrl":"10.3389/fcimb.2025.1509226","url":null,"abstract":"<p><strong>Background: </strong>Viral vaccines have been proven significant in protecting us against viral diseases such as COVID-19. To better understand and design viral vaccines, it is critical to systematically collect, annotate, and analyse various viral vaccines and identify enriched patterns from these viral vaccines.</p><p><strong>Methods: </strong>We systematically collected experimentally verified viral vaccines from the literature, manually annotated, and stored the information in the VIOLIN vaccine database. The annotated information included basic vaccine names, pathogens and diseases, vaccine components, vaccine formulations, and their induced host responses. Enriched patterns were identified from our systematical analysis of the viral vaccines and vaccine antigens.</p><p><strong>Results: </strong>A total of 2,847 viral vaccines against 95 viral species (including 72 RNA viral species and 23 DNA viral species) were collected, manually annotated, and stored in the VIOLIN vaccine database. These viral vaccines used 542 vaccine antigens. A taxonomical analysis found various DNA and RNA viruses covered by the viral vaccines. These vaccines target different viral life cycle stages (e.g., viral entry, assembly, exit, and immune evasion) as identified in top ranked human, animal vaccines, and HPV vaccines. The vaccine antigen proteins also show up in different virion locations in viruses such as HRSV vaccines. Both structural and non-structural viral proteins have been used for viral vaccine development. Protective vaccine antigens tend to have a protegenicity score of >85% based on the Vaxign-ML calculation, which measures predicted suitability for vaccine use. While predicted adhesins still have significantly higher chances of being protective antigens, only 21.42% of protective viral vaccine antigens were predicted to be adhesins. Furthermore, our Gene Ontology (GO) enrichment analysis using a customized Fisher's exact test identified many enriched patterns such as viral entry into the host cell, DNA/RNA/ATP/ion binding, and suppression of host type 1 interferon-mediated signaling pathway. The viral vaccines and their associated entities and relations are ontologically modeled and represented in the Vaccine Ontology (VO). A VIOLIN web interface was developed to support user friendly queries of viral vaccines.</p><p><strong>Discussion: </strong>Viral vaccines were systematically collected and annotated in the VIOLIN vaccine knowledgebase, and the analysis of these viral vaccines identified many insightful patterns.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1509226"},"PeriodicalIF":4.6,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maria Eduarda Souza Guerra, Giulia Destro, Brenda Vieira, Alice S Lima, Lucio Fabio Caldas Ferraz, Anders P Hakansson, Michelle Darrieux, Thiago Rojas Converso
{"title":"Corrigendum: <i>Klebsiella pneumoniae</i> biofilms and their role in disease pathogenesis.","authors":"Maria Eduarda Souza Guerra, Giulia Destro, Brenda Vieira, Alice S Lima, Lucio Fabio Caldas Ferraz, Anders P Hakansson, Michelle Darrieux, Thiago Rojas Converso","doi":"10.3389/fcimb.2025.1564010","DOIUrl":"https://doi.org/10.3389/fcimb.2025.1564010","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fcimb.2022.877995.].</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1564010"},"PeriodicalIF":4.6,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11840871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Distribution and frequency of genetic mutations in three insecticide targets in field populations of <i>Culex tritaeniorhynchus</i> in Mianyang City, Sichuan Province, China.","authors":"Hongwei Xie, Meilin Tang, Hongying Sun, Zhengzheng Huang, Mengmeng Dong, Xianying Wen","doi":"10.3389/fcimb.2025.1496849","DOIUrl":"10.3389/fcimb.2025.1496849","url":null,"abstract":"<p><p>Japanese encephalitis (JE) is an important mosquito borne infectious disease which is mainly transmitted by <i>Culex tritaeniorhynchus</i> Giles (1901) in China. At present, vector control remains an important means to prevent and control vector-borne diseases including JE. The development of insecticide resistance has seriously threatened the effectiveness of insecticide-based vector control programmes. Therefore, understanding insecticide resistance in the target pest is essential to inform evidence-based vector control. In Mianyang City of Sichuan Province of China, <i>Cx. tritaeniorhynchus</i> is the dominant mosquito species, and JE has been documented in this city. Unfortunately, there is little information on the status and underlying mechanisms of insecticide resistance in field populations of <i>Cx. tritaeniorhynchus</i>, the main JE vector in this region. In the study, a total of 314 adults of <i>Cx. tritaeniorhynchus</i>, collected from 6 sites across Mianyang City, were inspected for resistance-conferring mutations in three genes encoding voltage-gated sodium channel (VGSC), Gamma-aminobutyric acid (GABA) receptor Rdl subunit (Rdl), and acetylcholinesterase (AChE) by DNA Sanger sequencing. The results showed that the classical L1014F mutation in VGSC was distributed in all the 6 populations at varying frequencies from 16.98% to 27.78%, and the frequency of F455W mutation in AChE was extremely high (97.06%-100%). Notably, the conserved mutations A296S and V327I previously reported in the Rdl of some other species of mosquitoes were discovered in <i>Cx. tritaeniorhynchus</i> for the first time. The frequency of the resistant Rdl 296S allele was 62.04% to 94.00%, while the V327I mutation was present at a much lower frequency ranging from 0.93% to 1.8%. Overall, the prevalent co-existence of resistance-conferring mutations in multiple insecticide target proteins in <i>Cx. tritaeniorhynchus</i> populations in Mianyang City indicates a worrying status of insecticide resistance, and suggests that it is highly required to monitor the phenotypic resistance of <i>Cx. tritaeniorhynchus</i> on a regular basis.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1496849"},"PeriodicalIF":4.6,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11839803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rui Zhao, Guilun He, Lin Xiang, Melinda Ji, Rongheng He, Xudong Wei
{"title":"Metagenomic next-generation sequencing assists in the diagnosis of visceral leishmaniasis in non-endemic areas of China.","authors":"Rui Zhao, Guilun He, Lin Xiang, Melinda Ji, Rongheng He, Xudong Wei","doi":"10.3389/fcimb.2025.1517046","DOIUrl":"10.3389/fcimb.2025.1517046","url":null,"abstract":"<p><strong>Introduction: </strong>Leishmaniasis, a protozoan disease caused by infection by <i>Leishmania</i>, is a critical issue in Asia, South America, East Africa, and North Africa. With 12 million cases globally, leishmaniasis is one of the most serious neglected tropical diseases worldwide. Direct identification of infected tissues is currently the primary method of diagnosis; however, the low sensitivity and inconvenience of microscopic examination in detecting amastigotes, parasitic manifestations of <i>Leishmania</i>, leads to the possibility of misdiagnosis, delayed diagnosis, and underdiagnosis.</p><p><strong>Methods: </strong>With the development of metagenomic nextgeneration sequencing (mNGS) technology for pathogen identification, it is possible to detect specific nucleic acid sequences characteristic of <i>Leishmania</i> parasites, which opens new avenues for the more accurate diagnosis of leishmaniasis. In this study, we report two cases of leishmaniasis from Henan Province, China, in which <i>Leishmania</i> parasites were identified using mNGS technology, massively expediting diagnosis and treatment.</p><p><strong>Results: </strong>Our report demonstrates that the mNGS method is applicable to peripheral blood samples (PB), which are far more readily available in clinical settings, in addition to bone marrow aspirate samples (BM), which are traditionally used for diagnosis of visceral leishmaniasis.</p><p><strong>Conclusion: </strong>Our report validates the efficacy of mNGS technology as a rapid and accurate method of diagnosis for leishmaniasis.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1517046"},"PeriodicalIF":4.6,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11839618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Inhibition of early EHDV2-Ibaraki infection steps in bovine cells by endosome alkalinization or ikarugamycin, but not by blockage of individual endocytic pathways.","authors":"Maya Malka, Inbar Czaczkes, Shlomi Kashkash, Shirel Shachar, Eran Bacharach, Marcelo Ehrlich","doi":"10.3389/fcimb.2025.1494200","DOIUrl":"10.3389/fcimb.2025.1494200","url":null,"abstract":"<p><p>The Epizootic hemorrhagic disease virus (EHDV), an orbivirus, is the etiological factor of a fatal hemorrhagic disease of wild ruminants. A subset of EHDV serotypes, including the Ibaraki strain of EHDV2 (EHDV2-Ibaraki), infect and cause disease in cattle, thus posing a potential threat to livestock. As a member of the Sedoreoviridae family, the EHDV particle is devoid of a membrane envelope and is predicted to employ endocytic pathways for infection. However, the degree of dependence of EHDV2-Ibaraki on specific internalization pathways while infecting bovine cells (its natural host) is unknown. The endosome alkalinizing agent ammonium chloride blocked EHDV2-Ibaraki infection of Madin-Darby Bovine Kidney (MDBK) cells with dependence on its time of addition, suggesting the criticality of endosomal pH for the completion of early stages of infection. Treatment of cells within the alkalinization-sensitive window (i.e., before endosomal processing) with inhibitors of actin polymerization, macropinocytosis (amiloride), or dynamin GTPase activity (dynasore or dynole), or with the cholesterol-depleting agent methyl-β-cyclodextrin, failed to reduce EHDV2-Ibaraki infection. In contrast, in this same treatment time frame, ikarugamycin potently inhibited infection. Moreover, ikarugamycin inhibited interferon induction in infected cells and induced the accumulation of enlarged Rab7- and lamtor4-decorated vacuoles, suggesting its ability to block viral processing and modify late-endosome compartments. Notably, ikarugamycin treatment at initial infection stages, augmented the infection of MDBK cells with the vesicular stomatitis virus while inhibiting infection with bluetongue virus serotype 8. Together, our results point to differential antiviral effects of ikarugamycin on viruses dependent on distinct sets of endosomes for entry/processing.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1494200"},"PeriodicalIF":4.6,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11839642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Renato M S de Lima, Luana K R Leão, Luana C Martins, Adelaide da C Fonseca Passos, Evander de J Oliveira Batista, Anderson M Herculano, Karen R H M Oliveira
{"title":"Unveiling new perspectives about the onset of neurological and cognitive deficits in cerebral malaria: exploring cellular and neurochemical mechanisms.","authors":"Renato M S de Lima, Luana K R Leão, Luana C Martins, Adelaide da C Fonseca Passos, Evander de J Oliveira Batista, Anderson M Herculano, Karen R H M Oliveira","doi":"10.3389/fcimb.2025.1506282","DOIUrl":"10.3389/fcimb.2025.1506282","url":null,"abstract":"<p><p>Cerebral malaria is the most severe and lethal complication caused by <i>Plasmodium falciparum</i> infection, leading to critical neurological impairments and long-term cognitive, behavioral, and neurological sequelae in survivors, particularly affecting children under the age of five. Various hypotheses have been proposed to explain the neurological syndrome associated to cerebral malaria condition, including vascular occlusion and sequestration, cytokine storm or inflammatory response, or a combination of these mechanisms and despite extensive research and a growing range of scientific information, the precise pathophysiological mechanism remains poorly understood. In this sense, this review aims to explore the neurological impairment in cerebral malaria and elucidate novel mechanisms to explain the severity of this disease. Recent evidence implicates glutamate and glutamatergic pathways in the onset of cerebral malaria, alongside the impairments in the metabolic activity of other molecules such as dopamine and kynurenic acid. These neurotransmitters pathways may play a crucial role in the pathogenesis of cerebral malaria, potentially interacting with other molecular players. By enhancing our understanding in the pathophysiology of cerebral malaria, this article seeks to explore new hypotheses regarding the involvement of neurotransmitters and their interactions with other molecular targets, thereby contributing to the overall pathology of cerebral malaria.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1506282"},"PeriodicalIF":4.6,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11839640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Pediatric bacterial meningitis in southern China: analysis of 838 cases.","authors":"Lianfeng Chen, Wen-Lin Wu, Yuanyuan Gao, Xiaojing Li, Sida Yang, Huici Liang, Kelu Zheng, Yani Zhang, Haixia Zhu, Yang Tian, Bingwei Peng, Haisheng Lin, Xiuying Wang, Shuyao Ning, Yinyan Gan, Chi Hou, Yinting Liao, Huiling Sheng, Wen-Xiong Chen","doi":"10.3389/fcimb.2025.1481716","DOIUrl":"10.3389/fcimb.2025.1481716","url":null,"abstract":"<p><strong>Objective: </strong>This work aims to study the clinical features and risk factors of children with bacterial meningitis (BM) in southern China.</p><p><strong>Methods: </strong>Clinical data of children with BM between 2012 and 2018 from one national center were analyzed retrospectively.</p><p><strong>Results: </strong>A total of 838 patients (male/female = 1.8:1) were enrolled, with 90.6% under 1 year old. Common symptoms included fever, seizure, lethargy, vomiting, anorexia, poor feeding, and irritability. Most patients initially exhibited typical cerebrospinal fluid (CSF) changes of BM, including elevated white blood cell count, increased protein levels, and decreased glucose concentration. Some initially atypical cases showed typical changes after about 1 week. Furthermore, 38.7% of the patients had positive bacterial cultures of blood or CSF, with <i>Streptococcus agalactiae</i>, <i>Escherichia coli</i>, and <i>Streptococcus pneumoniae</i> commonly seen. Moreover, 92.0% of the patients were graded five Glasgow outcome scale (GOS) points at discharge. Differences in symptoms, pathogens, CSF results, brain MRI, and GOS points were observed across age groups (neonate [29 days, 12 months) and aged ≥12 months). Fatality rate was 1.9%, and 10.7% of survivors had neurological sequelae. Recurrent BM was rare (1.6%) but notable in patients with CSF fistula or immunodeficiency. Risk factors for intensive care unit admission, brain parenchymal involvement, subdural effusion, and hearing impairment were identified.</p><p><strong>Conclusion: </strong>Most pediatric BM patients in southern China were under 1 year old, with more distribution in male patients and some age-related differences in clinical features and outcomes. Recurrent BM is rare but more likely in patients with conditions such as CSF fistula or immunodeficiency. Most patients have favorable outcomes, with a low fatality rate and around 10% of the survivors experiencing neurological sequelae. Several clinical risk factors were identified.</p>","PeriodicalId":12458,"journal":{"name":"Frontiers in Cellular and Infection Microbiology","volume":"15 ","pages":"1481716"},"PeriodicalIF":4.6,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11835870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143457468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}