Hao Liu, Wenjing Wang, Yang Zhang, Fuchun Wang, Junyi Duan, Tao Huang, Xiaojie Huang, Tong Zhang
{"title":"Global perspectives on smallpox vaccine against monkeypox: a comprehensive meta-analysis and systematic review of effectiveness, protection, safety and cross-immunogenicity.","authors":"Hao Liu, Wenjing Wang, Yang Zhang, Fuchun Wang, Junyi Duan, Tao Huang, Xiaojie Huang, Tong Zhang","doi":"10.1080/22221751.2024.2387442","DOIUrl":"10.1080/22221751.2024.2387442","url":null,"abstract":"<p><p>A large outbreak of monkeypox occurred in 2022, and most people lack immunity to orthopoxvirus. Smallpox vaccination is essential for preventing further smallpox outbreaks. This study evaluated the effectiveness, protection, safety, and cross-immunogenicity of smallpox vaccine in preventing monkeypox infection. PubMed, Embase, Scopus, and Web of Science were searched from database inception to 10 March 2024. We included studies involving \"monkeypox virus\" and \"vaccinations\", and excluded reviews, animal studies, and articles with missing or duplicate data. A total of 37 studies with 57,693 participants were included in the final analysis. The effectiveness data showed that monkeypox infection rates were lower in the smallpox-vaccinated group than in the unvaccinated group (risk ratio [RR]: 0.46; 95% confidence interval [CI]: 0.31-0.68). The protection data showed that smallpox vaccination effectively reduced the risk of severe monkeypox infection (RR: 0.61; 95% CI: 0.42-0.87). Third-generation vaccines showed greater efficacy (RR: 0.36, 95% CI: 0.22-0.56) than first-generation vaccines. The number of doses of smallpox vaccine has no significant effect on monkeypox. Safety data showed that adverse reactions after smallpox vaccination were mainly mild and included local erythema, swelling, induration, itching, and pain. Meanwhile, we found that smallpox vaccination could induce the production of neutralizing antibodies against monkeypox. Our findings offer compelling evidence supporting the clinical application of the smallpox vaccine for preventing monkeypox and advocate that high-risk groups should be prioritized for receiving one dose of the smallpox vaccine if the vaccine stockpile is low.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2387442"},"PeriodicalIF":8.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11332295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855205","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}
Laura Marcos-Villar, Beatriz Perdiguero, María López-Bravo, Carmen Zamora, Laura Sin, Enrique Álvarez, Carlos Óscar S Sorzano, Pedro J Sánchez-Cordón, José M Casasnovas, David Astorgano, Juan García-Arriaza, Shubaash Anthiya, Mireya L Borrajo, Gustavo Lou, Belén Cuesta, Lorenzo Franceschini, Josep L Gelpí, Kris Thielemans, Marta Sisteré-Oró, Andreas Meyerhans, Felipe García, Ignasi Esteban, Núria López-Bigas, Montserrat Plana, María J Alonso, Mariano Esteban, Carmen Elena Gómez
{"title":"Heterologous mRNA/MVA delivering trimeric-RBD as effective vaccination regimen against SARS-CoV-2: COVARNA Consortium.","authors":"Laura Marcos-Villar, Beatriz Perdiguero, María López-Bravo, Carmen Zamora, Laura Sin, Enrique Álvarez, Carlos Óscar S Sorzano, Pedro J Sánchez-Cordón, José M Casasnovas, David Astorgano, Juan García-Arriaza, Shubaash Anthiya, Mireya L Borrajo, Gustavo Lou, Belén Cuesta, Lorenzo Franceschini, Josep L Gelpí, Kris Thielemans, Marta Sisteré-Oró, Andreas Meyerhans, Felipe García, Ignasi Esteban, Núria López-Bigas, Montserrat Plana, María J Alonso, Mariano Esteban, Carmen Elena Gómez","doi":"10.1080/22221751.2024.2387906","DOIUrl":"10.1080/22221751.2024.2387906","url":null,"abstract":"<p><p>Despite the high efficiency of current SARS-CoV-2 mRNA vaccines in reducing COVID-19 morbidity and mortality, waning immunity and the emergence of resistant variants underscore the need for novel vaccination strategies. This study explores a heterologous mRNA/Modified Vaccinia virus Ankara (MVA) prime/boost regimen employing a trimeric form of the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein compared to a homologous MVA/MVA regimen. In C57BL/6 mice, the RBD was delivered during priming via an mRNA vector encapsulated in nanoemulsions (NE) or lipid nanoparticles (LNP), followed by a booster with a replication-deficient MVA-based recombinant virus (MVA-RBD). This heterologous mRNA/MVA regimen elicited strong anti-RBD binding and neutralizing antibodies (BAbs and NAbs) against both the ancestral SARS-CoV-2 strain and different variants of concern (VoCs). Additionally, this protocol induced robust and polyfunctional RBD-specific CD4 and CD8 T cell responses, particularly in animals primed with mLNP-RBD. In K18-hACE2 transgenic mice, the LNP-RBD/MVA combination provided complete protection from morbidity and mortality following a live SARS-CoV-2 challenge compared with the partial protection observed with mNE-RBD/MVA or MVA/MVA regimens. Although the mNE-RBD/MVA regimen only protects half of the animals, it was able to induce antibodies with Fc-mediated effector functions besides NAbs. Moreover, viral replication and viral load in the respiratory tract were markedly reduced and decreased pro-inflammatory cytokine levels were observed. These results support the efficacy of heterologous mRNA/MVA vaccine combinations over homologous MVA/MVA regimen, using alternative nanocarriers that circumvent intellectual property restrictions of current mRNA vaccine formulations.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2387906"},"PeriodicalIF":8.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11313003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859284","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}
Yuan Zhang, Lingying Fang, Zongmei Wang, Chengguang Zhang, Jianqing Zhao, Hakimeh Baghaei Daemi, Mai Zhang, Liwen Yuan, Xiaohu Han, Linfeng Li, Zhen F Fu, Ming Zhou, Ling Zhao
{"title":"A modified recombinant adenovirus vector containing dual rabies virus G expression cassettes confers robust and long-lasting humoral immunity in mice, cats, and dogs.","authors":"Yuan Zhang, Lingying Fang, Zongmei Wang, Chengguang Zhang, Jianqing Zhao, Hakimeh Baghaei Daemi, Mai Zhang, Liwen Yuan, Xiaohu Han, Linfeng Li, Zhen F Fu, Ming Zhou, Ling Zhao","doi":"10.1080/22221751.2023.2300461","DOIUrl":"10.1080/22221751.2023.2300461","url":null,"abstract":"<p><p>During the COVID-19 epidemic, the incidence of rabies has increased in several countries, especially in remote and disadvantaged areas, due to inadequate surveillance and declining immunization coverage. Multiple vaccinations with inactivated rabies virus vaccines for pre- or post-exposure prophylaxis are considered inefficient, expensive and impractical in developing countries. Herein, three modified human recombinant adenoviruses type 5 designated Adv-RVG, Adv-E1-RVG, and Adv-RVDG, carrying rabies virus G (RVG) expression cassettes in various combinations within <i>E1</i> or <i>E3</i> genomic regions, were constructed to serve as rabies vaccine candidates. Adv-RVDG mediated greater RVG expression both <i>in vitro</i> and <i>in vivo</i> and induced a more robust and durable humoral immune response than the rabies vaccine strain SAD-L16, Adv-RVG, and Adv-E1-RVG by more effectively activating the dendritic cells (DCs) - follicular helper T (Tfh) cells - germinal centre (GC) / memory B cells (MBCs) - long-lived plasma cells (LLPCs) axis with 100% survival after a lethal RABV challenge in mice during the 24-week study period. Similarly, dogs and cats immunized with Adv-RVDG showed stronger and longer-lasting antibody responses than those vaccinated with a commercial inactivated rabies vaccine and showed good tolerance to Adv-RVDG. In conclusion, our study demonstrated that simultaneous insertion of protective antigens into the <i>E1</i> and <i>E3</i> genomic regions of adenovirus vector can significantly enhance the immunogenicity of adenoviral-vectored vaccines, providing a theoretical and practical basis for the subsequent development of multivalent and multi-conjugated vaccines using recombinant adenovirus platform. Meanwhile, our data suggest Adv-RVDG is a safe, efficient, and economical vaccine for mass-coverage immunization.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2300461"},"PeriodicalIF":8.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10810672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139073578","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 attenuated African swine fever vaccine HLJ/18-7GD provides protection against emerging prevalent genotype II variants in China.","authors":"Zilong Wang, Jiwen Zhang, Fang Li, Zhenjiang Zhang, Weiye Chen, Xianfeng Zhang, Encheng Sun, Yuanmao Zhu, Renqiang Liu, Xijun He, Zhigao Bu, Dongming Zhao","doi":"10.1080/22221751.2023.2300464","DOIUrl":"10.1080/22221751.2023.2300464","url":null,"abstract":"<p><p>Genetic changes have occurred in the genomes of prevalent African swine fever viruses (ASFVs) in the field in China, which may change their antigenic properties and result in immune escape. There is usually poor cross-protection between heterogonous isolates, and, therefore, it is important to test the cross-protection of the live attenuated ASFV vaccines against current prevalent heterogonous isolates. In this study, we evaluated the protective efficacy of the ASFV vaccine candidate HLJ/18-7GD against emerging isolates. HLJ/18-7GD provided protection against a highly virulent variant and a lower lethal isolate, both derived from genotype II Georgia07-like ASFV and isolated in 2020. HLJ/18-7GD vaccination prevented pigs from developing ASF-specific clinical signs and death, decreased viral shedding via the oral and rectal routes, and suppressed viral replication after challenges. However, HLJ/18-7GD vaccination did not provide solid cross-protection against genotype I NH/P68-like ASFV challenge in pigs. HLJ/18-7GD vaccination thus shows great promise as an alternative strategy for preventing and controlling genotype II ASFVs, but vaccines providing cross-protection against different ASFV genotypes may be needed in China.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2300464"},"PeriodicalIF":8.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10810661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139073595","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}
Seung-Gyu Jang, Young-Il Kim, Mark Anthony B Casel, Jeong Ho Choi, Ju Ryeon Gil, Rare Rollon, Eun-Ha Kim, Se-Mi Kim, Ho Young Ji, Dong Bin Park, Jungwon Hwang, Jae-Woo Ahn, Myung Hee Kim, Min-Suk Song, Young Ki Choi
{"title":"HA N193D substitution in the HPAI H5N1 virus alters receptor binding affinity and enhances virulence in mammalian hosts.","authors":"Seung-Gyu Jang, Young-Il Kim, Mark Anthony B Casel, Jeong Ho Choi, Ju Ryeon Gil, Rare Rollon, Eun-Ha Kim, Se-Mi Kim, Ho Young Ji, Dong Bin Park, Jungwon Hwang, Jae-Woo Ahn, Myung Hee Kim, Min-Suk Song, Young Ki Choi","doi":"10.1080/22221751.2024.2302854","DOIUrl":"10.1080/22221751.2024.2302854","url":null,"abstract":"<p><p>During the 2021/2022 winter season, we isolated highly pathogenic avian influenza (HPAI) H5N1 viruses harbouring an amino acid substitution from Asparagine(N) to Aspartic acid (D) at residue 193 of the hemagglutinin (HA) receptor binding domain (RBD) from migratory birds in South Korea. Herein, we investigated the characteristics of the N193D HA-RBD substitution in the A/CommonTeal/Korea/W811/2021[CT/W811] virus by using recombinant viruses engineered via reverse genetics (RG). A receptor affinity assay revealed that the N193D HA-RBD substitution in CT/W811 increases α2,6 sialic acid receptor binding affinity. The rCT/W811-HA<sub>193N</sub> virus caused rapid lethality with high virus titres in chickens compared with the rCT/W811-HA<sub>193D</sub> virus, while the rCT/W811-HA<sub>193D</sub> virus exhibited enhanced virulence in mammalian hosts with multiple tissue tropism. Surprisingly, a ferret-to-ferret transmission assay revealed that rCT/W811-HA<sub>193D</sub> virus replicates well in the respiratory tract, at a rate about 10 times higher than that of rCT/W811-HA<sub>193N</sub>, and all rCT/W811-HA<sub>193D</sub> direct contact ferrets were seroconverted at 10 days post-contact. Further, competition transmission assay of the two viruses revealed that rCT/W811-HA<sub>193D</sub> has enhanced growth kinetics compared with the rCT/W811-HA<sub>193N</sub>, eventually becoming the dominant strain in nasal turbinates. Further, rCT/W811-HA<sub>193D</sub> exhibits high infectivity in primary human bronchial epithelial (HBE) cells, suggesting the potential for human infection. Taken together, the HA-193D containing HPAI H5N1 virus from migratory birds showed enhanced virulence in mammalian hosts, but not in avian hosts, with multi-organ replication and ferret-to-ferret transmission. Thus, this suggests that HA-193D change increases the probability of HPAI H5N1 infection and transmission in humans.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2302854"},"PeriodicalIF":13.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10840603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139377373","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":"Transmission of fluoroquinolones resistance among multidrug-resistant tuberculosis in Shanghai, China: a retrospective population-based genomic epidemiology study.","authors":"Minjuan Li, Yangyi Zhang, Zheyuan Wu, Yuan Jiang, Ruoyao Sun, Jinghui Yang, Jing Li, Honghua Lin, Rui Zhang, Qi Jiang, Lili Wang, Xiaocui Wu, Fangyou Yu, Jianhui Yuan, Chongguang Yang, Xin Shen","doi":"10.1080/22221751.2024.2302837","DOIUrl":"10.1080/22221751.2024.2302837","url":null,"abstract":"<p><p>Fluoroquinolones (FQ) are essential for the treatment of multidrug-resistant tuberculosis (MDR-TB). The FQ resistance (FQ-R) rate in MDR-TB in China and its risk factors remain poorly understood. We conducted a retrospective, population-based genomic epidemiology study of MDR-TB patients in Shanghai, China, from 2009 to 2018. A genomic cluster was defined as strains with genetic distances ≤ 12 single nucleotide polymorphisms. The transmitted FQ-R was defined as the same FQ resistance-conferring mutations shared by ≥ 2 strains in a genomic cluster. We used multivariable logistic regression analysis to identify the risk factors for drug resistance. Among the total 850 MDR-TB patients included in the study, 72.8% (619/850) were male, the median age was 39 (interquartile range 28, 55) years, 52.7% (448/850) were migrants, and 34.5% (293/850) were previously treated patients. Most of the MDR-TB strains belong to the Beijing lineage (91.7%, 779/850). Overall, the genotypic resistance rate of FQ was 34.7% (295/850), and 47.1% (139/295) FQ-R patients were in genomic clusters, of which 98 (33.2%, 98/295) were presumed as transmitted FQ-R. Patients with treatment-naïve (aOR = 1.84; 95% CI: 1.09, 3.16), diagnosed in a district-level hospital (aOR = 2.69; 95% CI: 1.56, 4.75), and streptomycin resistance (aOR = 3.69; 95% CI: 1.65, 9.42) were significantly associated with the transmission of FQ-R. In summary, the prevalence of FQ-R among MDR-TB patients was high in Shanghai, and at least one-third were transmitted. Enforced interventions including surveillance of FQ drug susceptibility testing and screening among MDR-TB before initiation of treatment were urgently needed.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2302837"},"PeriodicalIF":8.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10810664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139416589","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":"Effectiveness of a broad-spectrum bivalent mRNA vaccine against SARS-CoV-2 variants in preclinical studies.","authors":"Jing Lu, Shudan Tan, Hao Gu, Kunpeng Liu, Wei Huang, Zhaoli Yu, Guoliang Lu, Zihan Wu, Xiaobo Gao, Jinghua Zhao, Zongting Yao, Feng Yi, Yantao Yang, Hu Wang, Xue Hu, Mingqing Lu, Wei Li, Hui Zhou, Hang Yu, Chao Shan, Jinzhong Lin","doi":"10.1080/22221751.2024.2321994","DOIUrl":"10.1080/22221751.2024.2321994","url":null,"abstract":"<p><p>Vaccines utilizing modified messenger RNA (mRNA) technology have shown robust protective efficacy against SARS-CoV-2 in humans. As the virus continues to evolve in both human and non-human hosts, risk remains that the performance of the vaccines can be compromised by new variants with strong immune escape abilities. Here we present preclinical characterizations of a novel bivalent mRNA vaccine RQ3025 for its safety and effectiveness in animal models. The mRNA sequence of the vaccine is designed to incorporate common mutations on the SARS-CoV-2 spike protein that have been discovered along the evolutionary paths of different variants. Broad-spectrum, high-titer neutralizing antibodies against multiple variants were induced in mice (BALB/c and K18-hACE2), hamsters and rats upon injections of RQ3025, demonstrating advantages over the monovalent mRNA vaccines. Effectiveness in protection against several newly emerged variants is also evident in RQ3025-vaccinated rats. Analysis of splenocytes derived cytokines in BALB/c mice suggested that a Th1-biased cellular immune response was induced by RQ3025. Histological analysis of multiple organs in rats following injection of a high dose of RQ3025 showed no evidence of pathological changes. This study proves the safety and effectiveness of RQ3025 as a broad-spectrum vaccine against SARS-CoV-2 variants in animal models and lays the foundation for its potential clinical application in the future.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2321994"},"PeriodicalIF":13.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10906132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139912342","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}
Céline Nourrisson, Rose-Anne Lavergne, Maxime Moniot, Florent Morio, Philippe Poirier
{"title":"<i>Enterocytozoon bieneusi,</i> a human pathogen.","authors":"Céline Nourrisson, Rose-Anne Lavergne, Maxime Moniot, Florent Morio, Philippe Poirier","doi":"10.1080/22221751.2024.2406276","DOIUrl":"10.1080/22221751.2024.2406276","url":null,"abstract":"<p><p>Although brought to the forefront in the 1980s with the AIDS pandemic, microsporidia infecting humans are still little known. <i>Enterocytozoon bieneusi</i>, by far the most frequent microsporidia species causing diseases in humans, is responsible for intestinal illness in both non- and immunocompromised patients. This species presents an astonishing genetic diversity with more than 500 genotypes described, some of which have a strong zoonotic potential. Indeed, <i>E. bieneusi</i> infects a broad array of hosts, from wild to domestic animals. This emerging eukaryotic pathogen has thus been associated with foodborne/waterborne outbreaks. Several molecular assays have been developed to enhance its diagnosis or for epidemiological purposes, providing valuable new data. Here, we propose an overview of the current knowledge on this major species among the microsporidia, so far rather neglected in human medicine.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2406276"},"PeriodicalIF":8.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11428314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282193","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}
Mohammad Khaja Mafij Uddin, Andrea Maurizio Cabibbe, Rumana Nasrin, Arash Ghodousi, Fahim Alam Nobel, S M Mazidur Rahman, Shahriar Ahmed, Md Fahim Ather, S M Abdur Razzaque, Md Abu Raihan, Pronab Kumar Modak, Jean Luc Berland, Wayne Van Gemert, Sardar Munim Ibna Mohsin, Daniela Maria Cirillo, Sayera Banu
{"title":"Targeted next-generation sequencing of <i>Mycobacterium tuberculosis</i> from patient samples: lessons learned from high drug-resistant burden clinical settings in Bangladesh.","authors":"Mohammad Khaja Mafij Uddin, Andrea Maurizio Cabibbe, Rumana Nasrin, Arash Ghodousi, Fahim Alam Nobel, S M Mazidur Rahman, Shahriar Ahmed, Md Fahim Ather, S M Abdur Razzaque, Md Abu Raihan, Pronab Kumar Modak, Jean Luc Berland, Wayne Van Gemert, Sardar Munim Ibna Mohsin, Daniela Maria Cirillo, Sayera Banu","doi":"10.1080/22221751.2024.2392656","DOIUrl":"10.1080/22221751.2024.2392656","url":null,"abstract":"<p><p>Lack of appropriate early diagnostic tools for drug-resistant tuberculosis (DR-TB) and their incomplete drug susceptibility testing (DST) profiling is concerning for TB disease control. Existing methods, such as phenotypic DST (pDST), are time-consuming, while Xpert MTB/RIF (Xpert) and line probe assay (LPA) are limited to detecting resistance to few drugs. Targeted next-generation sequencing (tNGS) has been recently approved by WHO as an alternative approach for rapid and comprehensive DST. We aimed to investigate the performance and feasibility of tNGS for detecting DR-TB directly from clinical samples in Bangladesh. pDST, LPA and tNGS were performed among 264 sputum samples, either rifampicin-resistant (RR) or rifampicin-sensitive (RS) TB cases confirmed by Xpert assay. Resistotypes of tNGS were compared with pDST, LPA and composite reference standard (CRS, resistant if either pDST or LPA showed a resistant result). tNGS results revealed higher sensitivities for rifampicin (RIF) (99.3%), isoniazid (INH) (96.3%), fluoroquinolones (FQs) (94.4%), and aminoglycosides (AMGs) (100%) but comparatively lower for ethambutol (76.6%), streptomycin (68.7%), ethionamide (56.0%) and pyrazinamide (50.7%) when compared with pDST. The sensitivities of tNGS for INH, RIF, FQs and AMGs were 93.0%, 96.6%, 90.9%, and 100%, respectively and the specificities ranged from 91.3 to 100% when compared with CRS. This proof of concept study, conducted in a high-burden setting demonstrated that tNGS is a valuable tool for identifying DR-TB directly from the clinical specimens. Its feasibility in our laboratory suggests potential implementation and moving tNGS from research settings into clinical settings.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2392656"},"PeriodicalIF":8.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11348811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970892","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}
Pallavi Singh, Pratap Vydyam, Tiffany Fang, Karel Estrada, Luis Miguel Gonzalez, Ricardo Grande, Madelyn Kumar, Sakshar Chakravarty, Vincent Berry, Vincent Ranwez, Bernard Carcy, Delphine Depoix, Sergio Sánchez, Emmanuel Cornillot, Steven Abel, Loic Ciampossin, Todd Lenz, Omar Harb, Alejandro Sanchez-Flores, Estrella Montero, Karine G Le Roch, Stefano Lonardi, Choukri Ben Mamoun
{"title":"Insights into the evolution, virulence and speciation of <i>Babesia MO1</i> and <i>Babesia divergens</i> through multiomics analyses.","authors":"Pallavi Singh, Pratap Vydyam, Tiffany Fang, Karel Estrada, Luis Miguel Gonzalez, Ricardo Grande, Madelyn Kumar, Sakshar Chakravarty, Vincent Berry, Vincent Ranwez, Bernard Carcy, Delphine Depoix, Sergio Sánchez, Emmanuel Cornillot, Steven Abel, Loic Ciampossin, Todd Lenz, Omar Harb, Alejandro Sanchez-Flores, Estrella Montero, Karine G Le Roch, Stefano Lonardi, Choukri Ben Mamoun","doi":"10.1080/22221751.2024.2386136","DOIUrl":"10.1080/22221751.2024.2386136","url":null,"abstract":"<p><p>Babesiosis, caused by protozoan parasites of the genus <i>Babesia</i>, is an emerging tick-borne disease of significance for both human and animal health. <i>Babesia</i> parasites infect erythrocytes of vertebrate hosts where they develop and multiply rapidly to cause the pathological symptoms associated with the disease. The identification of new <i>Babesia</i> species underscores the ongoing risk of zoonotic pathogens capable of infecting humans, a concern amplified by anthropogenic activities and environmental changes. One such pathogen, <i>Babesia MO1</i>, previously implicated in severe cases of human babesiosis in the United States, was initially considered a subspecies of <i>B. divergens</i>, the predominant agent of human babesiosis in Europe. Here we report comparative multiomics analyses of <i>B. divergens</i> and <i>B. MO1</i> that offer insight into their biology and evolution. Our analysis shows that despite their highly similar genomic sequences, substantial genetic and genomic divergence occurred throughout their evolution resulting in major differences in gene functions, expression and regulation, replication rates and susceptibility to antiparasitic drugs. Furthermore, both pathogens have evolved distinct classes of multigene families, crucial for their pathogenicity and adaptation to specific mammalian hosts. Leveraging genomic information for <i>B. MO1</i>, <i>B. divergens</i>, and other members of the Babesiidae family within Apicomplexa provides valuable insights into the evolution, diversity, and virulence of these parasites. This knowledge serves as a critical tool in preemptively addressing the emergence and rapid transmission of more virulent strains.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2386136"},"PeriodicalIF":8.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11370697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987660","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}