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Genotypic diversity and antimicrobial resistance determinants in Salmonella Typhi isolated from children living in informal settlements in Nairobi, Kenya
IF 4.8 2区 医学
International Journal of Infectious Diseases Pub Date : 2025-03-01 DOI: 10.1016/j.ijid.2024.107390
Miss Susan Kavai , Dr Cecilia Mbae , Dr Sylvia Omulo , Prof Julius Oyugi , Prof Samuel Kariuki
{"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}
引用次数: 0
Antiviral Therapeutics Discovery for Enterovirus D68.
IF 4.8 2区 医学
International Journal of Infectious Diseases Pub Date : 2025-03-01 DOI: 10.1016/j.ijid.2025.107818
Prof Justin Jang H Chu
{"title":"Antiviral Therapeutics Discovery for Enterovirus D68.","authors":"Prof Justin Jang H Chu","doi":"10.1016/j.ijid.2025.107818","DOIUrl":"10.1016/j.ijid.2025.107818","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Enterovirus D68 (EV-D68) can cause a spectrum of clinical symptoms from mild respiratory symptoms to severe disease which can lead to hospitalization and even fatality in the immunocompromised, the elderly, and young children. To date, there are no effective antiviral successfully developed for enterovirus infection and the current understanding on pathogenesis is limited, which has resulted in the persistent circulation and outbreaks across the globe.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;An immunofluorescence-based phenotypic high-throughput antiviral screen was performed on both RD and H1299 cells, where 7,987 compounds across nine commercially-available drug libraries were screened for antiviral activity against Enterovirus D68 (EV-D68) strain US/KY/14-18953. Using a hit threshold of 50% inhibition and a toxicity threshold of nuclei count &gt; 1000, 178 hits were identified. These hits were further filtered for novelty and potency, which led to the validation of 12 compounds. MARVAS DF01 was selected for subsequent experiments due to its high efficacy (IC50: 1.804 µM).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;MARVAS DF01 treatment of EV-D68 infected cells potently reduced viral protein and viral genomic RNA levels. The time-of-addition, time-of-removal, and entry bypass studies showed that MARVAS DF01 acts in the post-entry stages of EV-D68 replication, specifically between 4 to 6 hours post-infection. Transfecting a Nanoluciferase viral replicon containing a truncated viral 3D protein still resulted in a luminescence reduction, indicating that MARVAS DF01 affects viral protein translation. Following serial passaging of EV-D68 in the presence of MARVAS DF01, no resistant mutants were found after 18 passages, suggesting the target of MARVAS DF01 to be a host factor. To elucidate the specific target, siRNA knockdown of the four currently known host targets of MARVAS DF01 was performed, from which ULK1 and ULK2 were identified to be involved in EV-D68 replication. As these two proteins are canonically known as part of the autophagy pathway, MARVAS DF01 was investigated for its role in EV-D68-induced autophagy. Through western blot and immunofluorescence staining, the LC3-II/LC3-I ratio and number of LC3 puncta-positive cells increased upon EV-D68 infection, indicating autophagy induction in infected cells. MARVAS DF01 treatment reversed this phenomenon, suggesting its mechanism of inhibition to be through the autophagy pathway. Additionally, MARVAS DF01 is a broad-spectrum enterovirus antiviral, inhibiting the replication of representative viruses from Enterovirus A-D and Rhinovirus A. MARVAS DF01 also reduced EV-D68 replication primary human nasal epithelial cells.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Discussion&lt;/h3&gt;&lt;div&gt;Our research has taken a leap into the identification of novel antivirals for EV-D68 and highlight the gap that necessitates further research to devise novel broad spectrum treatment approaches and modalities to thwart","PeriodicalId":14006,"journal":{"name":"International Journal of Infectious Diseases","volume":"152 ","pages":"Article 107818"},"PeriodicalIF":4.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520464","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}
引用次数: 0
Cholera Outbreak in Chienge District, Luapula Province, Zambia- 31st May – 9th June 2023: Re-emerging threat
IF 4.8 2区 医学
International Journal of Infectious Diseases Pub Date : 2025-03-01 DOI: 10.1016/j.ijid.2024.107433
Miss Tebello Kolobe
{"title":"Cholera Outbreak in Chienge District, Luapula Province, Zambia- 31st May – 9th June 2023: Re-emerging threat","authors":"Miss Tebello Kolobe","doi":"10.1016/j.ijid.2024.107433","DOIUrl":"10.1016/j.ijid.2024.107433","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Cholera remains a public health threat in Zambia, particularly in hotspot areas like Chienge district in Luapula Province, where the most recent previous outbreak was recorded in 2017. An outbreak of cholera in Chienge was first suspected on May 02, 2023, and confirmed on May 08, 2023. By May 18, 2023, the district had recorded 47 cases. This study aimed to describe cases, identify the cause, and risk factors, and propose control measures.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;An outbreak investigation followed by a 1: 2 matched case-control study were conducted. Suspected cases were individuals aged ≥2 years in the Lunchinda catchment area, presenting with acute watery diarrhoea with or without vomiting or signs of dehydration from April 28 to June 09, 2023. Confirmed cases involved isolation of vibrio cholerae O1 or 0139 from stool samples through culture. Cases and controls were matched by age and sex, with controls from the same household or neighbourhood. A structured questionnaire was used for interviews. The district is situated along the Luapula River and Lake Mweru, and has a total population of 189,893 that mainly depends on fishing as their main source of living. We conducted a descriptive analysis, calculated the case fatality rate (CFR), and applied Conditional logistic regression to determine odds ratios (OR) with 95% confidence interval in R.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Between April 2018 to June 09, 2023, a total of 79 cases were recorded, with 24 lab-confirmed 01 (23 Inaba, 1 Ogawa) species and one community death (CFR: 1.27%). The overall attack rate was 3 cases per 1,000 population. Approximately 80% of the case patients clustered along the lake. All the cases were detected in the health facilities, and 92% exhibited severe dehydration. From 67 cases and 134 controls, none were vaccinated against cholera. The main water source was the lake (41%). The absence of hand washing stations (OR: 2.3, CI: 1.1-4.9), and chlorine before the outbreak (OR: 6.3, CI: 1.3-30.8) were significantly associated with cholera.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Discussion&lt;/h3&gt;&lt;div&gt;The outbreak was linked to Vibrio cholerae O1, Inaba serotype. This community lacks safe water, sanitation, and hygiene (WASH) services as it is not under the administrative jurisdiction of the district. Both sexes were equally susceptible. Although the 1.2% fatality rate indicates effective management, it slightly surpasses WHO's threshold, possibly due to late health-seeking behaviours. Unknown vaccination status highlights gaps in coverage since the district conducted Cholera vaccination in the recent past. Risk factors like water source and treatment practices showed varied significance, emphasizing hand hygiene's crucial role.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;The outbreak was primarily caused by Inaba serotype. CFR was slightly above the WHO recommendation. Unavailability of chlorine and hand washing stations were the significant risk fact","PeriodicalId":14006,"journal":{"name":"International Journal of Infectious Diseases","volume":"152 ","pages":"Article 107433"},"PeriodicalIF":4.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520662","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}
引用次数: 0
Monkeypox virus (MPXV) isolation from longitudinal samples of 11 patients to infer risk of onwards transmission
IF 4.8 2区 医学
International Journal of Infectious Diseases Pub Date : 2025-03-01 DOI: 10.1016/j.ijid.2024.107458
Dr Helen Callaby , Dr Janie Olver , Ms Kirsty Emery , Dr Kevin Richards , Dr Marian Killip , Dr Natalie Groves , Dr Jake Dunning , Professor Malcolm G Semple , Professor J Kenneth Baillie , Dr Tommy Rampling , Dr Catherine F Houlihan
{"title":"Monkeypox virus (MPXV) isolation from longitudinal samples of 11 patients to infer risk of onwards transmission","authors":"Dr Helen Callaby ,&nbsp;Dr Janie Olver ,&nbsp;Ms Kirsty Emery ,&nbsp;Dr Kevin Richards ,&nbsp;Dr Marian Killip ,&nbsp;Dr Natalie Groves ,&nbsp;Dr Jake Dunning ,&nbsp;Professor Malcolm G Semple ,&nbsp;Professor J Kenneth Baillie ,&nbsp;Dr Tommy Rampling ,&nbsp;Dr Catherine F Houlihan","doi":"10.1016/j.ijid.2024.107458","DOIUrl":"10.1016/j.ijid.2024.107458","url":null,"abstract":"<div><h3>Introduction</h3><div>Monkeypox virus (MPXV), a DNA virus in the genus Orthopoxvirus, causes the clinical disease mpox. Human-to-human transmission occurs, primarily through contact with infectious lesions. The cycle threshold (Ct) value at which mpox virus can be isolated varies in the literature. Clarification of a Ct that correlates reliably with MPXV infectivity would have significant implications for infection control measures. Persistent viral shedding of mpox is widely reported but what is less well described is the duration of infectious MPXV from patient samples, using virus isolation as proxy.</div></div><div><h3>Methods</h3><div>This is a retrospective study using 169 longitudinal stored clinical isolates from 11 patients with clade II mpox. The samples were inoculated into African green monkey kidney (Vero E6) cells, termed passage 1 (P1). The P1 cultures were incubated and monitored for cytopathic effects (CPE). Cultures were sampled on day 0 and 7 and underwent virus inactivation, nucleic acid extraction and MPXV-specific PCR to support CPE observations. A decrease in mean MPXV Ct values from day 0 to 7 correlates to an increase in MPXV nucleic acid production, indicative of MPXV replication.</div></div><div><h3>Results</h3><div>The sampling frame for these patients ranged from the swab of an asymptomatic contact 13 days prior to the onset of symptoms, to 109 days post the onset of symptoms. 98 samples had a detectable Ct on MPXV PCR at day 0 (Ct range 20.1 to 39.7) and virus was able to be isolated from 46.9% of these samples (46/98). The cycle threshold at which virus was able to be isolated ranged from 22.3 to 37.7. Median MPXV Ct value for which virus could be isolated was 30.7. The longest duration from MPXV culture positivity from diagnosis was 109 days, from a throat swab with a Ct value of 35.9. The sample was from a 40-50 year old man with poorly controlled HIV CD4+ T-lymphocyte count 57 cells/mm3. HIV viral load 52,800 copies/ML) who presented with an ulcerating rash affecting limbs and a necrotic tongue lesion. The median time from mpox diagnosis to culture negative was 11.5 days (range 2 to 109).</div></div><div><h3>Discussion</h3><div>The duration of the infectious period of MPXV during clinical mpox is currently unclear with a paucity of robust longitudinal culture data, particularly from hospitalised patients. The median time of isolation of 11.5 days would fit within the known threshold but was far exceeded in a single immunocompromised patient at 109 days.</div></div><div><h3>Conclusion</h3><div>MPXV was isolated at higher Ct values than the previously reported, potentially removing the reassurance of lack of “infectiousness” in a patient with a rising Ct on PCR. Immunocompromised patients may be infectious with MPXV for longer than those with a competent immune system and these patients may require longer isolation.</div></div>","PeriodicalId":14006,"journal":{"name":"International Journal of Infectious Diseases","volume":"152 ","pages":"Article 107458"},"PeriodicalIF":4.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520683","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}
引用次数: 0
Use of murine model to study virulence of epidemically significant Mycobacterium tuberculosis genotypes and to evaluate effectiveness of chemotherapy
IF 4.8 2区 医学
International Journal of Infectious Diseases Pub Date : 2025-03-01 DOI: 10.1016/j.ijid.2024.107416
Dr Igor Mokrousov , Prof. Tatiana Vinogradova , Dr. Marine Dogonadze , Dr. Natalia Zabolotnykh , Dr. Marina Dyakova , Dr. Dilyara Esmedlyaeva , Dr. Maria Vitovskaya , Dr Olga Rubtsova , Dr Sergei Chekrygin , Dr Anna Vyazovaya , Prof. Boris Ariel
{"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}
引用次数: 0
Investigating an agnostic metagenomic virus discovery tool and evaluating the performance of Ion Torrent versus Oxford Nanopore Technology sequencing
IF 4.8 2区 医学
International Journal of Infectious Diseases Pub Date : 2025-03-01 DOI: 10.1016/j.ijid.2024.107457
Ms Tshegofatso Mahlangu , Dr Tongai Maponga , Mr Martin Deijs , Prof Lia van der Hoek , Prof Gert van Zyl , Prof Davey Smith
{"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}
引用次数: 0
Species distribution, antibiotic susceptibility and clinical characteristics in Enterococcal bacteremia; experience from South India
IF 4.8 2区 医学
International Journal of Infectious Diseases Pub Date : 2025-03-01 DOI: 10.1016/j.ijid.2024.107403
Dr Vettakkara Niyas, Dr Rajalakshmi Ananthanarayanan, Dr Febeena Hussain
{"title":"Species distribution, antibiotic susceptibility and clinical characteristics in Enterococcal bacteremia; experience from South India","authors":"Dr Vettakkara Niyas,&nbsp;Dr Rajalakshmi Ananthanarayanan,&nbsp;Dr Febeena Hussain","doi":"10.1016/j.ijid.2024.107403","DOIUrl":"10.1016/j.ijid.2024.107403","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;While the incidence of Vancomycin-resistant Enterococci (VRE) infections in India remains lower than in other countries, recent reports indicate an upward trend. This study investigates the clinical characteristics and antibiotic susceptibility profile associated with Enterococcus bacteremia.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We conducted a retrospective analysis of patient records with Enterococcal bacteremia from January 2016 to December 2022 at our tertiary care center in Kerala, South India. For the detection of bacterial growth, BacT/AlLERT 3D instrument was used. Identification and antibiotic susceptibility were done by the VITEK-2 system.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;During the study period, we identified 214 unique Enterococcus isolates in blood cultures. The median age of patients was 62 years (interquartile range: 51-71 years), with males constituting 66% of the cases. The most prevalent comorbidity was diabetes, affecting 51% of patients (n=109), followed by chronic kidney disease in 27% (n=58), and chronic liver disease in 22% (n=48). Malignancies were present in 16% of patients (n=34), and 17% (n=36) experienced immunosuppression from either disease or medication. The primary sources of infection were genitourinary (17%, n=36) and intestinal (16%, n=35) tracts, with infective endocarditis (IE) observed in 7% (n=15).&lt;/div&gt;&lt;div&gt;E. faecalis was the predominant species, accounting for 50% of cases (n=107), followed by E. faecium at 39.5% (n=85). Other species included E. gallinarum (n=6), E. raffinose (n=4), E. durans (n=2), E. avium (n=2), and E. casseliflavus (n=1). Species identification was indeterminate in 6 isolates.&lt;/div&gt;&lt;div&gt;Among the E. faecalis isolates, 100% susceptibility was noted for vancomycin and linezolid, 95% for teicoplanin, 88% for penicillin, 86% for ampicillin, and 61% for gentamicin. For E. faecium, susceptibility rates were 95% for vancomycin and linezolid, 88% for teicoplanin, 36% for gentamicin, and only 11% for penicillin and ampicillin. Daptomycin was tested in 28 isolates, with 1 being resistant and 2 showing intermediate susceptibility. Among the 2 isolates that exhibited vancomycin and linezolid resistance, daptomycin remained susceptible.&lt;/div&gt;&lt;div&gt;Overall, 59% of patients improved, 30% expired, and 11% were discharged at their request and could not be followed up. Among the 95 patients with E. faecalis bacteremia, 67% survived, while among the 76 patients with E. faecium bacteremia, 64% survived. There was no statistically significant correlation between comorbidities, infection source, species, and clinical outcomes. Among those diagnosed with vancomycin-sensitive Enterococcus, almost one-third (29%) succumbed. Among the 4 patients diagnosed with VRE, 3 did not survive.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;Enterococcal bacteremia is associated with significant mortality, with approximately one-third of patients succumbing to the illness. However, vancomycin re","PeriodicalId":14006,"journal":{"name":"International Journal of Infectious Diseases","volume":"152 ","pages":"Article 107403"},"PeriodicalIF":4.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520879","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}
引用次数: 0
The hidden burden of enteric infections in British Columbia, Canada, 2005-2014
IF 4.8 2区 医学
International Journal of Infectious Diseases Pub Date : 2025-03-01 DOI: 10.1016/j.ijid.2024.107404
Dr Eleni Galanis , Dr. Eleni Galanis , Dimitra Panagiotoglou , Marsha Taylor
{"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}
引用次数: 0
The current landscape in antibiotic access and supply issues: a qualitative study with key experts and opinion leaders
IF 4.8 2区 医学
International Journal of Infectious Diseases Pub Date : 2025-03-01 DOI: 10.1016/j.ijid.2024.107391
Dr Esmita Charani , Dr Vrinda Nampoothiri , Dr Ritika Kondal , Dr Avaneesh Pandey , Dr Oluchi Mbamalu , Dr Jennifer Cohn , Dr Sanjeev Singh , Dr Nusrat Shafiq
{"title":"The current landscape in antibiotic access and supply issues: a qualitative study with key experts and opinion leaders","authors":"Dr Esmita Charani ,&nbsp;Dr Vrinda Nampoothiri ,&nbsp;Dr Ritika Kondal ,&nbsp;Dr Avaneesh Pandey ,&nbsp;Dr Oluchi Mbamalu ,&nbsp;Dr Jennifer Cohn ,&nbsp;Dr Sanjeev Singh ,&nbsp;Dr Nusrat Shafiq","doi":"10.1016/j.ijid.2024.107391","DOIUrl":"10.1016/j.ijid.2024.107391","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;There is an increasing lack of access to safe and effective antibiotics for human consumption. We investigated the main drivers for current antibiotic shortages and existing mitigation strategies undertaken in different regions.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Purposive sampling was used to identify stakeholders with expertise in antibiotic access and supply chains. Consented participants were interviewed using a piloted semi-structured interview guide that was developed using the PESTELI (political, economic, sociological, ecological, technological, legal, industry) framework. Analysis and data collection are iterative and recursive, using constant comparison. Theoretical sampling is being applied to develop categories until saturation is reached.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Between August 2023 and March 2024, 14 key stakeholders with local, national, and global roles in supply chain management (South Africa-7, UK-2, Sweden- 2, Netherlands-1, Belgium-1, USA-1) were interviewed. Political engagement on antibiotic shortages is reported to facilitate effective mitigation strategies, especially in areas where there is strong evidence of government investment. Political support manifests as legal measures for example in the EU and UK in supporting the response to shortages, giving rights to pharmacists to intervene through protocolized measures to use alternative agents, and negotiating with pharmaceutical companies for greater transparency on the challenges in manufacturing. Economic incentives are required at all levels and are currently missing. There is increasing monopolization of active pharmaceutical ingredients and raw materials in the pharmaceutical industry with a lack of information, partly due to technological insufficiency to gather appropriate data at scale across sectors for example on procurement in the community, for key antibiotics at high risk of being impacted by shortages. Sociological impacts and drivers of shortages include adopting appropriate communication to not cause panic buying and hoarding by organisations when there is an impending shortage and recognising the important role of a multidisciplinary response. The key stakeholders identified for developing mitigation strategies included pharmaceutical manufacturers, policymakers and regulators, and global organisations such as WHO. Mitigation strategies included moving stock between pharmacies, pharmacists being assigned to monitor antibiotic supply and shortages at the hospital level, and implementation of serious shortage protocols in the UK which enable pharmacists to dispense alternate antibiotics in case of shortages.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Discussion&lt;/h3&gt;&lt;div&gt;There is a need for improved communications regarding shortages from the suppliers and transparency about potential problems in the supply chain. We were not able to interview actors from the pharmaceutical industry due to their restrictions which was a limitation since ","PeriodicalId":14006,"journal":{"name":"International Journal of Infectious Diseases","volume":"152 ","pages":"Article 107391"},"PeriodicalIF":4.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520315","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}
引用次数: 0
Advanced HIV as a Neglected Disease
IF 4.8 2区 医学
International Journal of Infectious Diseases Pub Date : 2025-03-01 DOI: 10.1016/j.ijid.2024.107379
Joe Jarvis
{"title":"Advanced HIV as a Neglected Disease","authors":"Joe Jarvis","doi":"10.1016/j.ijid.2024.107379","DOIUrl":"10.1016/j.ijid.2024.107379","url":null,"abstract":"<div><div>Although HIV treatment coverage has increased substantially in recent years, the associated reductions in AIDS-related deaths have been smaller and slower than expected. The proportion of people with advanced HIV disease remains high: it is estimated that more than 4 million people have advanced HIV disease, and each year more than 600,000 of them are expected to die. Many of these deaths can be prevented. Until recently, advanced HIV was viewed as a problem of late presentation, so the solution was thought to be testing more people and diagnosing the disease earlier. Although late presentation remains problematic, however, advanced HIV is now predominantly seen among people who started care but were not effectively engaged or have disengaged, returning only when they're ill. This talk will discuss who is at risk for the worst outcomes; which infections lead to the greatest morbidity and mortality; new tools for diagnosing, preventing, and treating these conditions; and how systems could adapt to delivering these tools effectively.</div></div>","PeriodicalId":14006,"journal":{"name":"International Journal of Infectious Diseases","volume":"152 ","pages":"Article 107379"},"PeriodicalIF":4.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520319","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}
引用次数: 0
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