International Journal of Infectious Diseases最新文献

{"title":"Cholera case trends in Eastern Africa using surveillance data, 2007-2024","authors":"Dr Joy Ebonwu , Ms Dativa Aliddeki , Dr Judith Kose Otieno , Dr Lul Pout Riek , Ms Kyeng Mercy","doi":"10.1016/j.ijid.2024.107432","DOIUrl":"10.1016/j.ijid.2024.107432","url":null,"abstract":"<div><h3>Introduction</h3><div>Cholera is a public health threat in Africa, with an estimated 68,480 cases and 895 deaths reported across seven of 14 Member States in the Eastern region in 2023. Within the region, cholera outbreak has been protracted in the horn of Africa, with countries responding to the outbreak amid prolonged harsh drought, floods and complex humanitarian emergencies. In recent months, an upsurge in cases and deaths has been observed in the region, with five countries reporting active outbreaks this year. We describe the trend of cholera cases in Comoros, Ethiopia, Kenya, Somalia and Tanzania for 2007-2024.</div></div><div><h3>Methods</h3><div>Descriptive trend analysis of cholera case data for Comoros, Ethiopia, Kenya, Somalia and Tanzania, from 2007-2024, was performed. Data were obtained from the Event Management System of the Africa Centres for Disease Control and Prevention (2023-2024) and the Global Infectious Disease and Epidemiology Network (GIDEON) online resource for data (2007-2022). Water, Sanitation and Hygiene (WASH) data was sourced from WHO/UNICEF Joint Monitoring Program for WASH. The term 'cholera case' includes both confirmed and suspected.</div></div><div><h3>Results</h3><div>From 2007 to 5 April 2024, a total of 578,449 cholera cases and 8,514 deaths [case fatality rate (CFR): 1.5%] were reported from Comoros, Ethiopia, Kenya, Somalia and Tanzania. Somalia accounted for 55.2% (315,972) of the cases and 54.6% (4,700) of the corresponding deaths. The average CFR per year was 1.4%, ranging from 0.3% in 2014 to 2.4% in 2016. During the review period, notable geographical patterns that were triggered by climate change were observed. Somalia experienced annual cholera outbreaks beginning November and December and receding in May, with largest occurrences in 2011 (77,636 cases) and 2017 (75,414 cases). Widespread outbreaks occurred in Ethiopia from 2007-2010, with a high peak in 2009 (31,509 cases) and recently in 2023 (29,869 cases). For this year, cases in Kenya appear to be on the decline while Tanzania shows an increasing pattern. Comoros reported its first cholera outbreak since 2007 in February 2024 through a cross-border event with Tanzania. Ethiopia is among countries in Africa with the largest population practicing open defecation in 2022.</div></div><div><h3>Discussion</h3><div>The trend analysis underscores the persistent nature of cholera outbreak in the Eastern region. Climate change impacts the dynamics of the outbreak by limiting access to safe water and sanitation, and triggering increased cross-border movements. The average CFR per year surpassed the recommended <1% threshold.</div></div><div><h3>Conclusion</h3><div>The cholera response requires a regional multi-sectoral and coordination mechanism approach, given the same protracted nature and cross-border transmissions. Significant resources are needed to implement long-term WASH strategies. With the predicted above-normal rainfall for the ho","PeriodicalId":14006,"journal":{"name":"International Journal of Infectious Diseases","volume":"152 ","pages":"Article 107432"},"PeriodicalIF":4.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520661","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":"Innovative approach for the clinical development of a Chlamydia trachomatis vaccine through a human challenge model in women","authors":"Craig R. Cohen","doi":"10.1016/j.ijid.2025.107861","DOIUrl":"10.1016/j.ijid.2025.107861","url":null,"abstract":"<div><div><em>Chlamydia trachomatis</em> remains the most common sexually transmitted bacterial infection worldwide. Recent phase I trials of the <em>C. trachomatis</em> vaccine candidate CTH522 in women and men have shown that the adjuvanted and non-adjuvanted formulations are safe and elicit systemic (immunoglobulin G) and mucosal (immunoglobulin A) antibodies, as well as vaccine-specific cell-mediated immunity. In advance of a standard phase II randomized controlled trial to determine the vaccine's efficacy, this perspective advocates for a carefully and ethically designed human challenge model as an innovative approach to assess a vaccine's ability to prevent infection and its impact on tubal immunopathogenesis in breakthrough infections. Such models could accelerate vaccine development by providing critical insights, making it essential for stakeholders to consider this approach and expedite the long-awaited chlamydia vaccine.</div></div>","PeriodicalId":14006,"journal":{"name":"International Journal of Infectious Diseases","volume":"154 ","pages":"Article 107861"},"PeriodicalIF":4.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143541984","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":"Normalization of wastewater-based epidemiology data for pathogen surveillance: a case study of campus-wide SARS-CoV-2 surveillance at a South African university","authors":"Dr Rianita Van Onselen ,&nbsp;Ms Sinazo Zingani ,&nbsp;Dr Renee Street ,&nbsp;Prof Rabia Johnson ,&nbsp;Dr Sharlene Govender","doi":"10.1016/j.ijid.2024.107384","DOIUrl":"10.1016/j.ijid.2024.107384","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Wastewater-based epidemiology (WBE) has emerged as a valuable tool for monitoring community-level SARS-CoV-2 exposure during the COVID-19 pandemic. However, several limitations of WBE have been identified, which have hindered its wider application. One key challenge is interpreting pathogen incidence data meaningfully, considering that measured pathogen concentrations can be influenced by external factors such as dilution by greywater in combined sewer systems and the sampling method used. This study aimed to evaluate data normalization strategies for viral copy numbers measured in samples collected passively from sewer lines at a South African university.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Wastewater samples were collected weekly over a one-year period from sewer lines at seven on-campus sites at the Nelson Mandela University. Passive, 3D-printed, torpedo-style samplers containing standard medical gauze as adsorbent were deployed directly into sewer lines for 9 hours to interact with wastewater. The gauze was then retrieved from the samplers and solids were eluted into PBS with 0.05% Tween 80. Total RNA was subsequently extracted from the samples using the Qiagen RNeasy Powersoil kit, followed by quantification of the RNA concentration using a NanoDrop spectrophotometer. SARS-CoV-2 copy numbers were determined using RT-qPCR with primers and probes targeting two regions in the nucleocapsid gene, namely N1 and N2. RT-qPCR was also employed to quantify the copy numbers of two commonly used viral normalizers, namely aichi virus (AiV) and pepper mild mottle virus (PMMoV). SARS-CoV-2 copy numbers were then normalized against AiV and PMMoV copy numbers and against extracted RNA concentration. Normalized and unnormalized SARS-CoV-2 data were evaluated against clinical numbers using Spearman correlation to determine the most effective normalization strategy.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Normalization against AiV showed weak correlations with clinical case numbers (r=0.29), and AiV was not consistently detected in all samples. Normalizing SARS-CoV-2 data against PMMoV data improved correlations significantly when compared with unnormalized SARS-CoV-2 (r=0.67 vs r=0.44; P≤0.05). The strongest correlation with clinical case data was obtained when SARS-CoV-2 copy numbers were normalized against initial RNA concentrations (r=0.81; P≤0.05).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Discussion&lt;/h3&gt;&lt;div&gt;When employing passive sampling to collect wastewater samples for the quantification of pathogens for epidemiology, the traditionally used normalization strategies that apply community and physicochemical parameters and flow rates cannot be employed, especially in mixed grey- and blackwater systems. Normalizing against extracted RNA concentration is not affected by diet, takes into account dilution of pathogens by greywater and the variability in RNA extraction between samples, and improved the correlation between wastewater pathogen concentratio","PeriodicalId":14006,"journal":{"name":"International Journal of Infectious Diseases","volume":"152 ","pages":"Article 107384"},"PeriodicalIF":4.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520641","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":"Innovative methodological approach to assess dengue transmission: findings from the SERODEN study in Africa","authors":"Miss Anna Vicco ,&nbsp;Aboubacry Gaye ,&nbsp;Clare McCormack ,&nbsp;Belen Pedrique ,&nbsp;Anthony Afum-Adjei Awuah ,&nbsp;Christian Obirikorang ,&nbsp;Antoine Nkuba-Ndaye ,&nbsp;Paul Tshiminyi-Munkamba ,&nbsp;Moussa Dia ,&nbsp;Oumar Ndiaye ,&nbsp;Martine Guillerm ,&nbsp;Nicole S. Struck ,&nbsp;Shubham Shrivastava ,&nbsp;Cheikh Loucoubar ,&nbsp;Cheikh Talla ,&nbsp;Isabela Ribeiro ,&nbsp;Steve Ahuka-Mundeke ,&nbsp;John H. Amuasi ,&nbsp;Oumar Faye ,&nbsp;Christl A Donnelly ,&nbsp;Ilaria Dorigatti","doi":"10.1016/j.ijid.2024.107423","DOIUrl":"10.1016/j.ijid.2024.107423","url":null,"abstract":"<div><h3>Introduction</h3><div>A limited number of dengue seroprevalence surveys have been conducted across Africa, with only 21 studies reported to date. Implementing new surveys to assess dengue transmission can be costly, time-consuming and resource intensive. In SERODEN we developed new simulation-based methods to calculate the optimal number and age-distribution of existing blood samples –collected in the context of previous household and community-based surveys, most notably against SARS-CoV-2 – to be tested for dengue. We used three different assays, namely the enzyme-linked immunosorbent assay (ELISA) IgG type 1-4, ELISA IgG NS1 type 1-4 and Plaque Reduction Neutralization Test (PRNT) for the 4 dengue serotypes, to characterise age-specific seroprevalence and dengue transmission intensity in 19 locations across Senegal, the Democratic Republic of the Congo (DRC), and Ghana.</div></div><div><h3>Method</h3><div>We designed a simulation-based framework to inform serosurvey design when leveraging existing blood samples. We also developed a Bayesian approach to combine the results obtained from the different assays in unifying age-stratified seroprevalence and force of infection estimates, estimating and accounting for the tests’ specificity and sensitivity.</div></div><div><h3>Results</h3><div>Our simulation-based framework identified the optimal sample sizes and age-distribution of the available blood samples, and overall, we reduced the total number of samples required for testing by 20%. The age-group prioritised for testing depended on the expected transmission intensity, with younger age-groups targeted for testing in high transmission settings. By combining multiple tests, including IgG ELISA type 1-4, ELISA IgG NS1, and PRNTs, we were able to quantify the specificity and sensitivity of each test and the dengue transmission in different African settings.</div></div><div><h3>Discussion</h3><div>Our results unveiled significant heterogeneity in dengue transmission both within and across countries and underscored the endemic nature of dengue transmission in Senegal, DRC, and Ghana. The methods developed in the SERODEN study demonstrates the feasibility and benefits of utilising existing blood samples for the implementation of dengue serosurveys.</div></div><div><h3>Conclusion</h3><div>By leveraging existing resources and combining different tests, we can provide valuable insights into dengue transmission intensity in Africa, which sheds new light on the dengue infection burden and can help inform dengue surveillance.</div></div>","PeriodicalId":14006,"journal":{"name":"International Journal of Infectious Diseases","volume":"152 ","pages":"Article 107423"},"PeriodicalIF":4.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520681","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":"Recurrence of microfilaraemia after triple-drug therapy for lymphatic filariasis in Samoa: Recrudescence or reinfection?","authors":"Helen J. Mayfield ,&nbsp;Ramona Muttucumaru ,&nbsp;Benn Sartorius ,&nbsp;Sarah Sheridan ,&nbsp;Selina Ward ,&nbsp;Beatris Mario Martin ,&nbsp;Shannon M. Hedtke ,&nbsp;Robert Thomsen ,&nbsp;Satupaitea Viali ,&nbsp;Glen Fatupaito ,&nbsp;Colleen L. Lau ,&nbsp;Patricia M. Graves","doi":"10.1016/j.ijid.2025.107809","DOIUrl":"10.1016/j.ijid.2025.107809","url":null,"abstract":"<div><h3>Objectives</h3><div>Contrasting evidence is emerging on the long-term effectiveness of triple-drug therapy for elimination of lymphatic filariasis (LF) in the Pacific region. We evaluated the effectiveness of ivermectin, diethylcarbamazine and albendazole (IDA) for sustained clearance of microfilariae (Mf) in Samoa.</div></div><div><h3>Methods</h3><div>We enrolled two cohorts of Mf-positive participants. Cohort A were Mf-positive participants from 2018, who received directly observed triple-drug therapy in 2019 and were retested and retreated in 2023 and 2024. Cohort B were Mf-positive and treated in 2023 and retested in 2024. Participants were tested for LF antigen and Mf.</div></div><div><h3>Results</h3><div>In Cohort A, eight of the 14 participants from 2018/2019 were recruited in 2023; six were Mf-positive. In 2024, six participants were retested, and two were Mf-positive. Cohort B included eight participants, and two remained Mf-positive in 2024. Mf prevalence in 2023 for Cohort A (71.4%, 95% CI 29.0%-96.3%) was significantly higher than among their household members (12.0%, 95% CI 2.5%-31.2%).</div></div><div><h3>Conclusion</h3><div>One or two doses of directly observed IDA was not sufficient for sustained clearance of <em>Wuchereria bancrofti</em> Mf in Samoa. The high Mf prevalence in treated individuals compared to household members suggests recrudescence rather than reinfection.</div></div>","PeriodicalId":14006,"journal":{"name":"International Journal of Infectious Diseases","volume":"152 ","pages":"Article 107809"},"PeriodicalIF":4.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074409","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":"Genotypic diversity and antimicrobial resistance determinants in Salmonella Typhi isolated from children living in informal settlements in Nairobi, Kenya","authors":"Miss Susan Kavai ,&nbsp;Dr Cecilia Mbae ,&nbsp;Dr Sylvia Omulo ,&nbsp;Prof Julius Oyugi ,&nbsp;Prof Samuel Kariuki","doi":"10.1016/j.ijid.2024.107390","DOIUrl":"10.1016/j.ijid.2024.107390","url":null,"abstract":"<div><h3>Introduction</h3><div>Whole genome sequencing (WGS) is an important tool for disease diagnostics and identification of circulating multi-drug resistant (MDR) genotypes of enteric pathogens globally. In typhoid-endemic regions, WGS of Salmonella Typhi (S. Typhi) has identified haplotype 58 (H58) as one of the dominant MDR haplogroups. This case-control study reports on antimicrobial resistance (AMR) genes and genotypic diversity of S. Typhi from sick and asymptomatic children in Mukuru and Kibera informal settlements in Nairobi County.</div></div><div><h3>Methods</h3><div>From 2013 to 2018, children ≤ 16 years presenting to 4 health facilities in Nairobi County were recruited if they had a fever; ≥380C with or without diarrhea. Asymptomatic individuals (controls) who reported to the facilities for vaccinations and with non-typhoid-related symptoms were also recruited. Both groups provided stool samples that were subjected to culture and antimicrobial susceptibility testing for phenotypic analysis of AMR. S. Typhi isolates that showed resistance to ampicillin, co-trimoxazole, and chloramphenicol were considered as MDR and subjected to WGS. Deoxyribonucleic acid (DNA) of 90 S. Typhi isolates (44 from sick and 46 from asymptomatic individuals) was extracted for WGS. Sequencing was done using the Illumina Nextseq2000 platform. The generated raw reads were de novo assembled and pathogen-watch was used for analysis.</div></div><div><h3>Results</h3><div>Of the sequenced isolates, 60(69%) were confirmed to be S. Typhi. All of the S. Typhi belonged to the sequence Type 1 and genotype 4.3.1 (Haplotype 58). Out of the 60 S. Typhi strains 40(67%) were found to have plasmids, out of which 38(95%) had the IncHI1A/IncHI1B (R27) plasmids. The distribution of S. Typhi in sick and asymptomatic individuals was almost equal at 31(51%) and 30(49%). The 60 S. Typhi isolates were observed to have AMR determinants of 6 antibiotics with ampicillin (bla TEM-1D) as the most common, observed in 59 (98%) of the isolates. Point mutations conferring reduced susceptibility to quinolones were detected in 42 (70%) of S. Typhi isolates, 14(33%) gyrA_S83Y, and 28/42 (67%) gyrB_S464F.</div></div><div><h3>Discussion</h3><div>This study reports all MDR S. Typhi sequenced to belong to sequence Type 1. Genotype 4.3.1 (H58) was observed as the most dominant S. Typhi genotype among the symptomatic and asymptomatic individuals. Haplotype 58 is responsible for the spread of MDR phenotypes that carry on IncHI1 plasmids.</div></div><div><h3>Conclusion</h3><div>Circulation of H58 S. Typhi genotypes in Mukuru and Kibera informal settlements especially among asymptomatic individuals reiterates the need for mass vaccination as a control and prevention measure of Typhoid fever in urban informal settlements in Kenya.</div></div>","PeriodicalId":14006,"journal":{"name":"International Journal of Infectious Diseases","volume":"152 ","pages":"Article 107390"},"PeriodicalIF":4.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520314","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":"An optimized chikungunya virus trans-amplifying RNA vaccine candidate induces potent immune responses with only 1 ng of antigen encoding RNA","authors":"Dr Christin Schmidt ,&nbsp;Dr Florian Hastert ,&nbsp;Dr Tim Beissert ,&nbsp;Dr Ugur Sahin ,&nbsp;Dr Mario Perkovic ,&nbsp;Dr Barbara Schnierle","doi":"10.1016/j.ijid.2024.107445","DOIUrl":"10.1016/j.ijid.2024.107445","url":null,"abstract":"<div><h3>Introduction</h3><div>The human pathogenic chikungunya virus (CHIKV) has caused outbreaks in over 100 countries worldwide and is raising public health concern. Further spread by mosquito vectors due to globalization and climate change is expected. The symptoms of a CHIKV infection include fever, headache, myalgia, arthritis, and joint pain. Although the mortality rate is rather low, infections can result in debilitating arthralgia that can become chronic. Accordingly, we aim to explore potential CHIKV vaccine candidates.</div></div><div><h3>Methods</h3><div>Our first-generation CHIKV vaccine candidate was based on trans-amplifying RNA (taRNA), consisting of two RNAs: a non-replicating mRNA encoding for the CHIKV nonstructural proteins, forming the replicase complex and a trans-replicon (TR) RNA encoding the CHIKV envelope proteins. The TR-RNA is efficiently amplified by the replicase in trans leading to a high antigen expression and potent immune responses. To optimize our taRNA platform, we now simplified the TR-RNA to the essential elements by removing the subgenomic promoter and redesigning the 5’ untranslated region. Additionally, we formulated our vaccine candidates with lipid nanoparticles and evaluated several modifications. Humoral and cellular immune responses were assessed after prime-boost immunization of mice.</div></div><div><h3>Results</h3><div>First, we could prove in vitro that the respective antigen can now be directly translated from the STR-RNA as from a normal mRNA. However, as the conserved sequence elements were preserved, the STR-RNA was efficiently amplified by the CHIKV replicase. Here, the usage of only the envelope proteins led to a high protein expression, whereas the addition of the capsid protein allowed the release of virus-like particles. The LNP formulation of our taRNA vaccine candidate led to a 4.3-fold greater antibody titer compared to intradermal vaccination in saline. In comparison to the previous TR-RNA, the STR-RNA induced a further 4-fold increase in antibody titers. Here, in contrast to our previous results, all mice developed potent neutralizing antibody responses. Importantly, we could drastically reduce the taRNA dose. Neutralizing antibodies could be induced with as little as 1 ng STR-RNA and 5 ng STR-RNA were sufficient to protect all mice from a CHIKV challenge infection.</div></div><div><h3>Discussion</h3><div>The CHIKV is of increasing public health concern after its rapid global spread. In comparison to mRNA vaccines, the platform of taRNA allows to significantly reduce the required RNA doses for protective immunity. Nevertheless, the potential of taRNA as vaccine in humans still needs to be established in clinical trials.</div></div><div><h3>Conclusion</h3><div>In conclusion, taRNA represents a promising safe and efficient vaccination strategy for emerging infectious diseases.</div></div>","PeriodicalId":14006,"journal":{"name":"International Journal of Infectious Diseases","volume":"152 ","pages":"Article 107445"},"PeriodicalIF":4.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520573","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":"Use of murine model to study virulence of epidemically significant Mycobacterium tuberculosis genotypes and to evaluate effectiveness of chemotherapy","authors":"Dr Igor Mokrousov ,&nbsp;Prof. Tatiana Vinogradova ,&nbsp;Dr. Marine Dogonadze ,&nbsp;Dr. Natalia Zabolotnykh ,&nbsp;Dr. Marina Dyakova ,&nbsp;Dr. Dilyara Esmedlyaeva ,&nbsp;Dr. Maria Vitovskaya ,&nbsp;Dr Olga Rubtsova ,&nbsp;Dr Sergei Chekrygin ,&nbsp;Dr Anna Vyazovaya ,&nbsp;Prof. Boris Ariel","doi":"10.1016/j.ijid.2024.107416","DOIUrl":"10.1016/j.ijid.2024.107416","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;The clinical manifestations of tuberculosis (TB) in humans represent a complex interaction between the causative agent, Mycobacterium tuberculosis, and the immune response of the human host. Using the murine model, we compared virulence of M. tuberculosis strains of the medically significant genotypes and evaluated the effectiveness of anti-TB therapy and inflammatory response in infected mice.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;The C57BL/6 mice were infected with multidrug-resistant clinical M. tuberculosis strains of Beijing and LAM genotypes. Control groups were not treated and experimental groups received adequate treatment with moxifloxacin, linezolid, bedaquiline and perchlozone. After 2 and 5.5 months of therapy, groups of mice were euthanized and studied for bacterial load, histology, lung pathology, and biochemical markers of liver damage. Whole genome sequencing was performed on all bacterial isolates from the lungs of the treated mice and the obtained fastq files were analyzed using SAM-TB tool and Geneious package. This study was funded by Russian Science Foundation (grant 24-44-00004).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The anti-TB therapy reduced the inflammation and tuberculous lung damage in all groups of mice, even in those infected with the most virulent strain Beijing 396. A significant effect of the anti-TB therapy was observed at both time-point for all groups. The highest effectiveness of the therapy was observed in mice infected with the least virulent strains Beijing 6691 and LAM 7074. At the same time, in 3 out of 4 groups of treated mice (except for those infected with the low-virulent strain LAM 7074), a slight increase in bacterial load was recorded by the end of the 5.5-month course of therapy. High-coverage WGS analysis showed that no mutations associated with resistance to the administered drugs emerged after 5.5 months of treatment. The study of non-specific inflammatory response revealed the differently severe acute inflammation in mice infected with different strains.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Discussion&lt;/h3&gt;&lt;div&gt;The highest lung damage was observed in treated mice infected with Beijing 396, the lowest – in mice infected with low-virulent Beijing 6691 and LAM 7074. At the same time, the contrasting inflammatory responses were observed in mice infected with the LAM strains: the highest in those infected by highly-virulent strain 4542 (SIT266), the lowest – in mice infected with low-virulent strain 7074 (SIT252). Phylogenetically, these LAM strains belong to the genetically homogeneous LAM-RUS branch and their contrasting in vivo manifestation is noteworthy.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;Some of the observed differences between studied strains distinguish between low-virulent and highly-virulent strains irrespective of the genotype. On the other hand, some other features were common for the strains of the same genotype either Beijing or LAM and might correlate with deeply roo","PeriodicalId":14006,"journal":{"name":"International Journal of Infectious Diseases","volume":"152 ","pages":"Article 107416"},"PeriodicalIF":4.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520762","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 hidden burden of enteric infections in British Columbia, Canada, 2005-2014","authors":"Dr Eleni Galanis ,&nbsp;Dr. Eleni Galanis ,&nbsp;Dimitra Panagiotoglou ,&nbsp;Marsha Taylor","doi":"10.1016/j.ijid.2024.107404","DOIUrl":"10.1016/j.ijid.2024.107404","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;One in eight Canadians experiences an enteric infection annually. In British Columbia (BC), Canada significant risks of sequelae and death following laboratory-confirmed, reported enteric infections exist, including a 30 times higher risk of acute kidney injury (AKI) and a 4 times higher risk of inflammatory bowel disease (IBD). However, reported infections do not represent everyone who seeks care for these infections. Thus, we aimed to determine whether individuals who sought care for enteric infections, but for whom no laboratory-confirmed infection was reported, were also at risk for kidney, gastrointestinal, and rheumatological sequelae and death, in BC, Canada.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We conducted a retrospective cohort study of everyone registered in BC's health insurance program, 2005-2014 (n=5,819,344). The cohort was followed for ∼7.5 years/person, and included 40,523 individuals with 42,308 laboratory-confirmed, reported enteric infections. Individuals with a physician visit or hospitalization with an International Classification of Disease (ICD) code for enteric infection or non-specific acute gastroenteritis, but without a reported, laboratory-confirmed infection, were our case group. Sequelae and deaths (from all causes) were identified using administrative data and vital statistics. We estimated risks using adjusted hazard ratios (aHRs) from extended Cox regression models, adjusting for age, sex, comorbidities, and neighbourhood income. Our comparison group was those without any evidence of enteric infection, i.e., who never had a laboratory-confirmed reported enteric infection, nor any physician visits or hospitalizations with ICD codes for enteric infections, during the study.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;From 2005-2014, 238,116 people experienced 298,577 separate episodes where they sought medical care with an ICD code for enteric infection, with no accompanying laboratory-confirmation reported. For these individuals, the risk of AKI was 21.4 times higher (95% confidence interval [CI]: 20.7, 22.1) in the 90 days after seeking care, and the risk of hemolytic-uremic syndrome was 40.9 times higher (95% CI: 20.5, 81.5) in the 1-45 days. Their risks of IBD (aHR: 4.73, 95%CI: 4.44, 5.05), celiac disease (aHR: 3.98; 95%CI: 3.72, 4.26), and irritable bowel syndrome (aHR: 4.91, 95%CI: 4.71, 5.13) in the six months after seeking care were also significantly higher. The risks of ankylosing spondylitis, reactive arthritis, and anterior uveitis were smaller, but also significant. The risk of dying was 8.75 times higher (95% CI: 8.38, 9.14) in the 30 days following a physician visit or hospitalization.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Discussion&lt;/h3&gt;&lt;div&gt;The risks of sequelae and mortality is comparable regardless of whether individuals had a laboratory-confirmed, reported infection. These findings are consistent with those reported by others, demonstrating the validity of using administrative health data","PeriodicalId":14006,"journal":{"name":"International Journal of Infectious Diseases","volume":"152 ","pages":"Article 107404"},"PeriodicalIF":4.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520812","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":"Investigating an agnostic metagenomic virus discovery tool and evaluating the performance of Ion Torrent versus Oxford Nanopore Technology sequencing","authors":"Ms Tshegofatso Mahlangu ,&nbsp;Dr Tongai Maponga ,&nbsp;Mr Martin Deijs ,&nbsp;Prof Lia van der Hoek ,&nbsp;Prof Gert van Zyl ,&nbsp;Prof Davey Smith","doi":"10.1016/j.ijid.2024.107457","DOIUrl":"10.1016/j.ijid.2024.107457","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction and motivation&lt;/h3&gt;&lt;div&gt;Emerging and re-emerging viruses are a global health concern. Historically, such viruses have been identified through targeted approaches, which has been the gold standard in diagnosis. Unfortunately, these approaches are limited to known pathogens and thus inadequate for the monitoring of “unknown” viruses. Therefore, there is a need for a technology that can identify known, novel and unexpected viruses.&lt;/div&gt;&lt;div&gt;Virus discovery using copy deoxyribonucleic acid (cDNA) and amplified fragment length polymorphism (AFLP) (also called VIDISCA) is a metagenomics approach that non-specifically enriches for viral sequences and then uses next generation sequencing (NGS) for virus discovery. VIDISCA has been used for the discovery of a several previously unknown viruses, including human coronavirus (HCoV) NL63 and Ntwetwe virus.&lt;/div&gt;&lt;div&gt;VIDISCA has previously relied on Ion Torrent NGS, and we hypothesised that Oxford Nanopore Technology (ONT), which is easier to use, could be as effective as Ion Torrent sequencing. Therefore, we developed and validated VIDISCA with ONT and this compared to Ion Torrent NGS.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methodology&lt;/h3&gt;&lt;div&gt;A library made-up of different sample types was split into two identical libraries to sequence on the ONT and Ion Torrent platforms. The samples contained known viral pathogens which were blinded and treated as “unknown” samples for viral discovery. cDNA was synthesized with random primers from nucleic acid extracts that were depleted of rRNA complementary sequences. After second strand synthesis, DNA was digested with a restriction enzyme coupled with adaptor ligation, which served as priming sites for PCR enrichment. Templates are then sequenced, and output files were mapped against protein databases including human, mammal, insect, tick and avian virus sequences.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Findings&lt;/h3&gt;&lt;div&gt;The two NGS platforms performed similarly in identifying the pathogens in the prepared library that contained Human Mastadenovirus (HAdV), Human Immunodeficiency virus (HIV), Hepatitis E virus (HEV), HCoV-NL63 and a virus free sample. Neither the ONT nor Ion Torrent platforms sequenced the HAdV. Both platforms also missed HEV in one sample. All other viruses were successfully identified by both platforms. Overall, ONT performed similarly to Ion Torrent.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion and relevance&lt;/h3&gt;&lt;div&gt;VIDISCA performed on Ion Torrent and ONT sequencing platforms has displayed similar Results. ONT sequencing has the advantage of a more rapid turnaround and low sequencing footprint with a similar cost estimation.&lt;/div&gt;&lt;div&gt;Future plans include the testing of residual patient samples where some viruses are often undiagnosed (such as cerebrospinal fluid) as well as sentinel species (such as rats and shrews) as a part of pandemic preparedness and novel virus discovery. If necessary, additional work, such as genome primer walking, will be conducted for full-genome ch","PeriodicalId":14006,"journal":{"name":"International Journal of Infectious Diseases","volume":"152 ","pages":"Article 107457"},"PeriodicalIF":4.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520815","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}