Pub Date : 2024-09-17DOI: 10.1016/j.ijid.2024.107245
Aseervatham Anusha Amali , Kathirvel Paramasivam , Sharada Ravikumar , Zhaohong Tan , Shaun Seh Ern Loong , Kelvin Han Chung Chong , Alicia Ang , Jin Zhu , Suma Sathyanarayana Rao , Louis Yi Ann Chai
In subjects with peculiar susceptibility to severe infections by common pyogenic bacteria, mutations of interleukin-1 receptor-associated kinase proteins (IRAK)1 and IRAK4 had been identified. The IRAK kinases function as downstream signal transductors following the activation of pathogen recognition receptors. In two patients with sequential or repeated invasive infections: herpes simplex virus-triggered hemophagocytic lymphohistiocytosis with tuberculosis, and Streptococcus pneumoniae bacteremia with candidemia respectively, novel mutations of IRAK2 were identified. These mutations compromised the capacity to ubiquinate (or functionally modify) the signal adaptor tumor necrosis factor receptor-associated factor 6. The result is impairment of the cytokine tumor necrosis factor-alpha production. This susceptibility to a varied range of pathogens underlines a potential central role played by IRAK2 in mediating host defense in infectious diseases.
{"title":"Severe invasive infections linked to IRAK2 immune variants","authors":"Aseervatham Anusha Amali , Kathirvel Paramasivam , Sharada Ravikumar , Zhaohong Tan , Shaun Seh Ern Loong , Kelvin Han Chung Chong , Alicia Ang , Jin Zhu , Suma Sathyanarayana Rao , Louis Yi Ann Chai","doi":"10.1016/j.ijid.2024.107245","DOIUrl":"10.1016/j.ijid.2024.107245","url":null,"abstract":"<div><div>In subjects with peculiar susceptibility to severe infections by common pyogenic bacteria, mutations of interleukin-1 receptor-associated kinase proteins (IRAK)1 and IRAK4 had been identified. The IRAK kinases function as downstream signal transductors following the activation of pathogen recognition receptors. In two patients with sequential or repeated invasive infections: herpes simplex virus-triggered hemophagocytic lymphohistiocytosis with tuberculosis, and <em>Streptococcus pneumoniae</em> bacteremia with candidemia respectively, novel mutations of IRAK2 were identified. These mutations compromised the capacity to ubiquinate (or functionally modify) the signal adaptor tumor necrosis factor receptor-associated factor 6. The result is impairment of the cytokine tumor necrosis factor-alpha production. This susceptibility to a varied range of pathogens underlines a potential central role played by IRAK2 in mediating host defense in infectious diseases.</div></div>","PeriodicalId":14006,"journal":{"name":"International Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286404","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}
Pub Date : 2024-09-14DOI: 10.1016/j.ijid.2024.107243
Raghad Al-Abdwani , Ahmed Al Farsi , Matthew Zachariah , Badriya Al Adawi , Azza Al-Rashdi , Naga Ram Dhande , Nagi Elsidig , Zaid Alhinai
Q fever is a zoonosis with a worldwide distribution that is caused by the intracellular bacterium Coxiella burnetii. Although most infections in children are asymptomatic and self-limiting, some experience severe or chronic manifestations. Its manifestations in patients with sickle cell disease are unknown, as there are no reports currently. We report the case of a 4-year-old child with sickle cell disease who was admitted to the intensive care unit with fever, septic shock and fulminant hepatic failure secondary to hepatic sequestration crisis and intrahepatic cholestasis. Coxiella burnetii infection was confirmed by molecular and serologic assays. Empiric therapy with doxycycline had a significant impact on his course, and he made an excellent recovery despite requiring extensive life-supportive measures initially. This is the first report of Q fever in a patient with sickle cell disease, demonstrating its capability to manifest as acute sickle hepatopathy with critical illness.
{"title":"Septic shock and fulminant hepatic failure secondary to Q fever in a child with sickle cell disease: First case report","authors":"Raghad Al-Abdwani , Ahmed Al Farsi , Matthew Zachariah , Badriya Al Adawi , Azza Al-Rashdi , Naga Ram Dhande , Nagi Elsidig , Zaid Alhinai","doi":"10.1016/j.ijid.2024.107243","DOIUrl":"10.1016/j.ijid.2024.107243","url":null,"abstract":"<div><div>Q fever is a zoonosis with a worldwide distribution that is caused by the intracellular bacterium <em>Coxiella burnetii</em>. Although most infections in children are asymptomatic and self-limiting, some experience severe or chronic manifestations. Its manifestations in patients with sickle cell disease are unknown, as there are no reports currently. We report the case of a 4-year-old child with sickle cell disease who was admitted to the intensive care unit with fever, septic shock and fulminant hepatic failure secondary to hepatic sequestration crisis and intrahepatic cholestasis. <em>Coxiella burnetii</em> infection was confirmed by molecular and serologic assays. Empiric therapy with doxycycline had a significant impact on his course, and he made an excellent recovery despite requiring extensive life-supportive measures initially. This is the first report of Q fever in a patient with sickle cell disease, demonstrating its capability to manifest as acute sickle hepatopathy with critical illness.</div></div>","PeriodicalId":14006,"journal":{"name":"International Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286403","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}
Pub Date : 2024-09-11DOI: 10.1016/j.ijid.2024.107237
Samba O. Sow , Milagritos D. Tapia , Fadima C. Haidara , Fatoumata Diallo , Xi Han , Jingjing Chen , Lei Shi , Qing Yang , Bangwei Yu , Yalin Hu , Lin Yuan , Ge Liu , Silvia Grappi , Martina Monti , Simonetta Viviani , Min Ji , Chenliang Zhou
Objectives
ZR-202-CoV and ZR-202a-CoV are novel recombinant vaccines containing 25 µg of the prototype (Wuhan strain) or B.1.351 strain (Beta variant) SARS-CoV-2 S-protein expressed in CHO cells, respectively, adjuvanted with Al(OH)3 and CpG-ODN. We assessed their safety and immunogenicity in this Phase I, randomized, observer-blind, controlled study in Mali.
Design
Sixty healthy 18–55-year-old adults randomized 1:1:1 received two doses of ZR-202-CoV, ZR-202a-CoV, or ComirnatyⓇ 28 days apart. Primary outcome measures were solicited and unsolicited adverse events (AEs) including AESI (Adverse Events of Special Interest); secondary outcome was immunogenicity measured as SARS-CoV-2 specific neutralizing antibodies. Participants were followed up for 1 year.
Results
Injection site pain and headache were the most frequent solicited local and systemic AEs, respectively. No unsolicited AEs or SAEs related to vaccination were reported during the study period. Although most participants had detectable neutralizing antibodies at baseline robust immune responses were observed in all vaccine groups after the first dose with no further increase after the second dose. Cross-neutralizing antibody responses against Beta, Delta, and Omicron BA.5 variants were similar in magnitude after ZR-202-CoV, ZR-202a-CoV and ComirnatyⓇ.
Conclusions
Similar reactogenicity and immunogenicity profiles of ZR-202-CoV, ZR-202a-CoV and ComirnatyⓇ support further clinical investigation in a wider population.
{"title":"Safety, reactogenicity, and immunogenicity of ZR-202-CoV and ZR-202a-CoV recombinant vaccines compared with ComirnatyⓇ: A randomized, observer-blind, controlled, phase 1 study","authors":"Samba O. Sow , Milagritos D. Tapia , Fadima C. Haidara , Fatoumata Diallo , Xi Han , Jingjing Chen , Lei Shi , Qing Yang , Bangwei Yu , Yalin Hu , Lin Yuan , Ge Liu , Silvia Grappi , Martina Monti , Simonetta Viviani , Min Ji , Chenliang Zhou","doi":"10.1016/j.ijid.2024.107237","DOIUrl":"10.1016/j.ijid.2024.107237","url":null,"abstract":"<div><h3>Objectives</h3><div>ZR-202-CoV and ZR-202a-CoV are novel recombinant vaccines containing 25 µg of the prototype (Wuhan strain) or B.1.351 strain (Beta variant) SARS-CoV-2 S-protein expressed in CHO cells, respectively, adjuvanted with Al(OH)<sub>3</sub> and CpG-ODN. We assessed their safety and immunogenicity in this Phase I, randomized, observer-blind, controlled study in Mali.</div></div><div><h3>Design</h3><div>Sixty healthy 18–55-year-old adults randomized 1:1:1 received two doses of ZR-202-CoV, ZR-202a-CoV, or Comirnaty<sup>Ⓡ</sup> 28 days apart. Primary outcome measures were solicited and unsolicited adverse events (AEs) including AESI (Adverse Events of Special Interest); secondary outcome was immunogenicity measured as SARS-CoV-2 specific neutralizing antibodies. Participants were followed up for 1 year.</div></div><div><h3>Results</h3><div>Injection site pain and headache were the most frequent solicited local and systemic AEs, respectively. No unsolicited AEs or SAEs related to vaccination were reported during the study period. Although most participants had detectable neutralizing antibodies at baseline robust immune responses were observed in all vaccine groups after the first dose with no further increase after the second dose. Cross-neutralizing antibody responses against Beta, Delta, and Omicron BA.5 variants were similar in magnitude after ZR-202-CoV, ZR-202a-CoV and Comirnaty<sup>Ⓡ</sup>.</div></div><div><h3>Conclusions</h3><div>Similar reactogenicity and immunogenicity profiles of ZR-202-CoV, ZR-202a-CoV and Comirnaty<sup>Ⓡ</sup> support further clinical investigation in a wider population.</div></div>","PeriodicalId":14006,"journal":{"name":"International Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286401","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}
Pub Date : 2024-09-11DOI: 10.1016/j.ijid.2024.107240
Ili Margalit , Yael Weiss-Ottolenghi , Einat Panet , Victoria Indenbaum , Neta S. Zuckerman , Gili Joseph , Yovel Peretz , Noam Barda , Yaniv Lustig , Gili Regev-Yochay
Background
We describe an epidemiological investigation of a SARS-CoV-2-XBB.1 outbreak among healthcare workers (HCWs) returning from a 5-days educational tour abroad.
Methods
We prospectively followed participants for symptoms and sampled blood for neutralization assays of four SARS-CoV-2 variants (wild type, XBB, EG.5.1, and BA.2.86) at 1, 3, and 6 months after their return. When available, samples from the 3 months preceding the outbreak were also tested. We compared geometric mean titers (GMT) of neutralizing antibodies of infected versus uninfected HCWs and febrile versus afebrile infected HCWs.
Results
Nineteen (10%) of 181 HCWs were infected, all had mild COVID-19, 90% (17/19) had symptoms, and 16% (3/19) reported fever. Infected individuals tended to have lower pre-exposure XBB-neutralizing antibody titers (GMT of 32 versus 107 ID50, P = 0.248). Neutralization against XBB and newer subvariants peaked at 3 months and was higher among infected individuals (GMT 702 versus 156 [P < 0.001], 558 versus 163 [P = 0.001], and 558 vs. 182 [P = 0.002], ID50 for XBB, EG.5.1., and BA.2.86, respectively). By six months, these differences were no longer observed. Fever was positively associated with XBB neutralization (GMT 3474 versus 485, ID50 P = 0.005).
Conclusions
Recently infected individuals are protected from reinfection with newer subvariants. However, protection is likely short lived.
{"title":"SARS-CoV-2 Omicron XBB.1 variant outbreak in a defined cohort: an epidemiological investigation incorporating longitudinal assessment of humoral response","authors":"Ili Margalit , Yael Weiss-Ottolenghi , Einat Panet , Victoria Indenbaum , Neta S. Zuckerman , Gili Joseph , Yovel Peretz , Noam Barda , Yaniv Lustig , Gili Regev-Yochay","doi":"10.1016/j.ijid.2024.107240","DOIUrl":"10.1016/j.ijid.2024.107240","url":null,"abstract":"<div><h3>Background</h3><div>We describe an epidemiological investigation of a SARS-CoV-2-XBB.1 outbreak among healthcare workers (HCWs) returning from a 5-days educational tour abroad.</div></div><div><h3>Methods</h3><div>We prospectively followed participants for symptoms and sampled blood for neutralization assays of four SARS-CoV-2 variants (wild type, XBB, EG.5.1, and BA.2.86) at 1, 3, and 6 months after their return. When available, samples from the 3 months preceding the outbreak were also tested. We compared geometric mean titers (GMT) of neutralizing antibodies of infected versus uninfected HCWs and febrile versus afebrile infected HCWs.</div></div><div><h3>Results</h3><div>Nineteen (10%) of 181 HCWs were infected, all had mild COVID-19, 90% (17/19) had symptoms, and 16% (3/19) reported fever. Infected individuals tended to have lower pre-exposure XBB-neutralizing antibody titers (GMT of 32 versus 107 ID50, <em>P</em> = 0.248). Neutralization against XBB and newer subvariants peaked at 3 months and was higher among infected individuals (GMT 702 versus 156 [<em>P</em> < 0.001], 558 versus 163 [<em>P</em> = 0.001], and 558 vs. 182 [<em>P</em> = 0.002], ID50 for XBB, EG.5.1., and BA.2.86, respectively). By six months, these differences were no longer observed. Fever was positively associated with XBB neutralization (GMT 3474 versus 485, ID50 <em>P</em> = 0.005).</div></div><div><h3>Conclusions</h3><div>Recently infected individuals are protected from reinfection with newer subvariants. However, protection is likely short lived.</div></div>","PeriodicalId":14006,"journal":{"name":"International Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286402","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}
Pub Date : 2024-09-10DOI: 10.1016/j.ijid.2024.107238
Yiming Huang, Richard Long, Giovanni Ferrara, Mary Lou Egedahl, Alexander Doroshenko, Courtney Heffernan, Catherine Paulsen, Ryan Cooper, Angela Lau
Objectives
Although a “multisite” definition of disseminated tuberculosis (DTB) exists, there is limited evidence to support its use. Herein, we sought to generate that evidence.
Methods
We evaluated treatment outcomes and reporting requirements against two distinct definitions of DTB in a 15-year population-based cohort of consecutively diagnosed patients with tuberculosis (TB) in Canada. Definitions were combined in a multi-variable logistic regression to determine the risk factors for TB-related death in DTB.
Results
We applied two mutually exclusive definitions of DTB to our data set: 1. “strict” - TB disease associated with a positive TB culture in blood/bone marrow or TB disease associated with a miliary pattern on chest imaging and a positive TB culture or, 2. multisite - TB disease in two or more non-contiguous sites. Among 2877 notified patients with TB, 110 (3.8%) met the strict definition, whereas 168 (5.8%) met the multisite definition. Of all 278 patients with DTB, only 135 (48.6%) were notified as DTB using International Classification of Disease codes and only 66 (23.7%) were classified as DTB by Canada's Public Health Agency. Patients with DTB by either definition were less likely to achieve cure/treatment completion and more likely to die. The risk factors for a fatal outcome included extremes of age, Canadian birth, central nervous system involvement, and HIV co-infection.
Conclusion
Our findings support the combination of a strict and multisite definition of DTB for purposes of reporting consistency and investigational comparability.
{"title":"Refining the definition of miliary/disseminated tuberculosis in Canada","authors":"Yiming Huang, Richard Long, Giovanni Ferrara, Mary Lou Egedahl, Alexander Doroshenko, Courtney Heffernan, Catherine Paulsen, Ryan Cooper, Angela Lau","doi":"10.1016/j.ijid.2024.107238","DOIUrl":"10.1016/j.ijid.2024.107238","url":null,"abstract":"<div><h3>Objectives</h3><div>Although a “multisite” definition of disseminated tuberculosis (DTB) exists, there is limited evidence to support its use. Herein, we sought to generate that evidence.</div></div><div><h3>Methods</h3><div>We evaluated treatment outcomes and reporting requirements against two distinct definitions of DTB in a 15-year population-based cohort of consecutively diagnosed patients with tuberculosis (TB) in Canada. Definitions were combined in a multi-variable logistic regression to determine the risk factors for TB-related death in DTB.</div></div><div><h3>Results</h3><div>We applied two mutually exclusive definitions of DTB to our data set: 1<em>.</em> “strict” - TB disease associated with a positive TB culture in blood/bone marrow or TB disease associated with a miliary pattern on chest imaging and a positive TB culture or, 2. multisite - TB disease in two or more non-contiguous sites. Among 2877 notified patients with TB, 110 (3.8%) met the strict definition, whereas 168 (5.8%) met the multisite definition. Of all 278 patients with DTB, only 135 (48.6%) were notified as DTB using International Classification of Disease codes and only 66 (23.7%) were classified as DTB by Canada's Public Health Agency. Patients with DTB by either definition were less likely to achieve cure/treatment completion and more likely to die. The risk factors for a fatal outcome included extremes of age, Canadian birth, central nervous system involvement, and HIV co-infection.</div></div><div><h3>Conclusion</h3><div>Our findings support the combination of a strict and multisite definition of DTB for purposes of reporting consistency and investigational comparability.</div></div>","PeriodicalId":14006,"journal":{"name":"International Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286400","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}
Pub Date : 2024-09-07DOI: 10.1016/j.ijid.2024.107235
Israel David Duarte-Herrera , Cecilia López-Martínez , Raquel Rodríguez-García , Diego Parra , Paula Martín-Vicente , Sara M. Exojo-Ramirez , Karla Miravete-Lagunes , Lisardo Iglesias , Marcelino González-Iglesias , Margarita Fernández-Rodríguez , Marta Carretero-Ledesma , Inés López-Alonso , Juan Gómez , Eliecer Coto , Rebeca González Fernández , Belén Prieto García , Javier Fernández , Laura Amado-Rodríguez , Guillermo M. Albaiceta
Objectives
Host responses to infection are a major determinant of outcome. However, the existence of different response profiles in patients with endocarditis has not been addressed. Our objective was to apply transcriptomics to identify endotypes in patients with infective endocarditis.
Methods
A total of 32 patients with infective endocarditis were studied. Clinical data and blood samples were collected at diagnosis and RNA sequenced. Gene expression was used to identify two clusters (endocarditis endotype 1 [EE1] and endocarditis endotype 2 [EE2]). RNA sequencing was repeated after surgery. Transcriptionally active cell populations were identified by deconvolution. Differences between endotypes in clinical data, survival, gene expression, and molecular pathways involved were assessed. The identified endotypes were recapitulated in a cohort of COVID-19 patients.
Results
A total of 18 and 14 patients were assigned to EE1 and EE2, respectively, with no differences in clinical data. Patients assigned to EE2 showed an enrichment in genes related to T-cell maturation and a decrease in the activation of the signal transducer and activator of transcription protein family pathway, with higher counts of active T cells and lower counts of neutrophils. A total of 14 patients (nine in EE1 and five in EE2) were submitted to surgery. Surgery in EE2 patients shifted gene expression toward a EE1-like profile. In-hospital mortality was higher in EE1 (56% vs 14%, P = 0.027), with an adjusted hazard ratio of 12.987 (95% confidence interval 3.356-50). Translation of these endotypes to COVID-19 and non–COVID-19 septic patients yielded similar results in cell populations and outcome.
Conclusions
Gene expression reveals two endotypes in patients with acute endocarditis, with different underlying pathogenetic mechanisms, responses to surgery, and outcomes.
{"title":"Identification of host endotypes using peripheral blood transcriptomics in a prospective cohort of patients with endocarditis","authors":"Israel David Duarte-Herrera , Cecilia López-Martínez , Raquel Rodríguez-García , Diego Parra , Paula Martín-Vicente , Sara M. Exojo-Ramirez , Karla Miravete-Lagunes , Lisardo Iglesias , Marcelino González-Iglesias , Margarita Fernández-Rodríguez , Marta Carretero-Ledesma , Inés López-Alonso , Juan Gómez , Eliecer Coto , Rebeca González Fernández , Belén Prieto García , Javier Fernández , Laura Amado-Rodríguez , Guillermo M. Albaiceta","doi":"10.1016/j.ijid.2024.107235","DOIUrl":"10.1016/j.ijid.2024.107235","url":null,"abstract":"<div><h3>Objectives</h3><div>Host responses to infection are a major determinant of outcome. However, the existence of different response profiles in patients with endocarditis has not been addressed. Our objective was to apply transcriptomics to identify endotypes in patients with infective endocarditis.</div></div><div><h3>Methods</h3><div>A total of 32 patients with infective endocarditis were studied. Clinical data and blood samples were collected at diagnosis and RNA sequenced. Gene expression was used to identify two clusters (endocarditis endotype 1 [EE1] and endocarditis endotype 2 [EE2]). RNA sequencing was repeated after surgery. Transcriptionally active cell populations were identified by deconvolution. Differences between endotypes in clinical data, survival, gene expression, and molecular pathways involved were assessed. The identified endotypes were recapitulated in a cohort of COVID-19 patients.</div></div><div><h3>Results</h3><div>A total of 18 and 14 patients were assigned to EE1 and EE2, respectively, with no differences in clinical data. Patients assigned to EE2 showed an enrichment in genes related to T-cell maturation and a decrease in the activation of the signal transducer and activator of transcription protein family pathway, with higher counts of active T cells and lower counts of neutrophils. A total of 14 patients (nine in EE1 and five in EE2) were submitted to surgery. Surgery in EE2 patients shifted gene expression toward a EE1-like profile. In-hospital mortality was higher in EE1 (56% vs 14%, <em>P</em> = 0.027), with an adjusted hazard ratio of 12.987 (95% confidence interval 3.356-50). Translation of these endotypes to COVID-19 and non–COVID-19 septic patients yielded similar results in cell populations and outcome.</div></div><div><h3>Conclusions</h3><div>Gene expression reveals two endotypes in patients with acute endocarditis, with different underlying pathogenetic mechanisms, responses to surgery, and outcomes.</div></div>","PeriodicalId":14006,"journal":{"name":"International Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1201971224003060/pdfft?md5=31bc5e6eaf453be31b33bf20faeae6d8&pid=1-s2.0-S1201971224003060-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153975","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}
Pub Date : 2024-09-07DOI: 10.1016/j.ijid.2024.107215
Matthew J. Akiyama , Yury Khudyakov , Sumathi Ramachandran , Lindsey R. Riback , Maxwell Ackerman , Mercy Nyakowa , Leonard Arthur , John Lizcano , Josephine Walker , Peter Cherutich , Ann Kurth
Objectives
Hepatitis C virus (HCV) disproportionately affects people who inject drugs (PWID) worldwide. Despite carrying a high HCV burden, little is known about transmission dynamics in low- and middle-income countries.
Methods
We recruited PWID from Nairobi and coastal cities of Mombasa, Kilifi, and Malindi in Kenya at needle and syringe programs. Next-generation sequencing data from HCV hypervariable region 1 were analyzed using Global Hepatitis Outbreak and Surveillance Technology to identify transmission clusters.
Results
HCV strains belonged to genotype 1a (n = 64, 46.0%) and 4a (n = 72, 51.8%) and were mixed HCV/1a/4a (n = 3, 2.2%). HCV/1a was dominant (61.2%) in Nairobi, whereas HCV/4a was dominant in Malindi (85.7%) and Kilifi (60.9%), and both genotypes were evenly identified in Mombasa (45.3% for HCV/1a and 50.9% for HCV/4a). Global Hepatitis Outbreak and Surveillance Technology identified 11 transmission clusters involving 90 cases. Strains in the two largest clusters (n = 38 predominantly HCV/4a and n = 32 HCV/1a) were sampled from all four cities.
Conclusions
Transmission clusters involving 64.7% of cases indicate an effective sampling of major HCV strains circulating among PWID. Large clusters involving 77.8% of strains from Nairobi and Coast suggest successful introduction of two ancestral HCV/1a and HCV/4a strains to PWID, with widely spread progeny. The disruption of the country-wide transmission network is essential for HCV elimination.
{"title":"Widespread hepatitis C virus transmission network among people who inject drugs in Kenya","authors":"Matthew J. Akiyama , Yury Khudyakov , Sumathi Ramachandran , Lindsey R. Riback , Maxwell Ackerman , Mercy Nyakowa , Leonard Arthur , John Lizcano , Josephine Walker , Peter Cherutich , Ann Kurth","doi":"10.1016/j.ijid.2024.107215","DOIUrl":"10.1016/j.ijid.2024.107215","url":null,"abstract":"<div><h3>Objectives</h3><p>Hepatitis C virus (HCV) disproportionately affects people who inject drugs (PWID) worldwide. Despite carrying a high HCV burden, little is known about transmission dynamics in low- and middle-income countries.</p></div><div><h3>Methods</h3><p>We recruited PWID from Nairobi and coastal cities of Mombasa, Kilifi, and Malindi in Kenya at needle and syringe programs. Next-generation sequencing data from HCV hypervariable region 1 were analyzed using Global Hepatitis Outbreak and Surveillance Technology to identify transmission clusters.</p></div><div><h3>Results</h3><p>HCV strains belonged to genotype 1a (n = 64, 46.0%) and 4a (n = 72, 51.8%) and were mixed HCV/1a/4a (n = 3, 2.2%). HCV/1a was dominant (61.2%) in Nairobi, whereas HCV/4a was dominant in Malindi (85.7%) and Kilifi (60.9%), and both genotypes were evenly identified in Mombasa (45.3% for HCV/1a and 50.9% for HCV/4a). Global Hepatitis Outbreak and Surveillance Technology identified 11 transmission clusters involving 90 cases. Strains in the two largest clusters (n = 38 predominantly HCV/4a and n = 32 HCV/1a) were sampled from all four cities.</p></div><div><h3>Conclusions</h3><p>Transmission clusters involving 64.7% of cases indicate an effective sampling of major HCV strains circulating among PWID. Large clusters involving 77.8% of strains from Nairobi and Coast suggest successful introduction of two ancestral HCV/1a and HCV/4a strains to PWID, with widely spread progeny. The disruption of the country-wide transmission network is essential for HCV elimination.</p></div>","PeriodicalId":14006,"journal":{"name":"International Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1201971224002868/pdfft?md5=d5b933ca9ff3e33169f89f87934f5697&pid=1-s2.0-S1201971224002868-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055491","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}
Pub Date : 2024-09-06DOI: 10.1016/j.ijid.2024.107236
Yvonne Kamau , Mercy Tuwei , Caroline Wanjiku , Kelly Ominde , Mwanajuma Ngama , Jonathan Karisa , Lawrence Babu , Martha Muturi , Mwaganyuma Mwatasa , Jane Adetifa , Charlotte Kern , Urs Duthaler , Felix Hammann , Regina Rabinovich , Carlos Chaccour , Marta Ferreira Maia
Objectives
When malaria vectors consume ivermectin in a blood meal, their survival probability decreases, potentially reducing malaria transmission during mass drug administrations. However, questions remain regarding the optimal dosing. This study aimed to compare the mosquitocidal effect and pharmacokinetics of two-dose regimens of ivermectin for malaria vector control.
Design
We conducted an open-label randomized control trial in Kenya, staggered in blocks with sequential intervention groups and parallel controls. Participants were randomly assigned (2:1:1:1) using computer random-sequence generation, unstratified, with one block of six pharmacokinetics-only participants (single-dose ivermectin) and six blocks of four participants (3:1 intervention vs control), to receive single-dose ivermectin (400 mcg/kg, n = 12), three daily doses (3-day regimen 300 mcg/kg, n = 6), albendazole (400 mg, n = 6), or no treatment (negative control, n = 6). Our primary outcome was Anopheles gambiae survival (time-to-event [days]) after blood feeding up to 10 days after drug administration. We also evaluated pharmacokinetics (peak plasma and capillary blood concentration, areas under the plasma and capillary blood concentration-time curve from time of last administration to time of last observation, time to reach peak plasma and capillary blood concentration, terminal elimination half-life) up to 7 days after treatment.
Results
A total of 36 healthy volunteers aged 21-32 years were recruited into the study and followed up to completion, with two participants not attending the visit on day 28. All drug regimens were well-tolerated. Both regimens showed significant mosquitocidal effect in the first 7 days. At 10 days after treatment, the single dose presented superior longevity of effect (adjusted hazard ratio = 3.91; 95% confidence interval = 1.93-7.93; P <0.001) compared with the triple dose (adjusted hazard ratio = 1.79; 95% confidence interval = 0.88-3.62; P = 0.0.11). Albendazole had, overall, no mosquitocidal effect.
Conclusions
It is unclear why a single dose led to increased bio-efficacy compared with a triple dose. We recommend trials investigating ivermectin mass drug administrations for malaria control to consider single-dose ivermectin. A single-dose regimen is also expected to present additional operational advantages compared with a 3-day regimen, leading to improved programmatic suitability.
{"title":"Mosquitocidal efficacy and pharmacokinetics of single-dose ivermectin versus three-day dose regimen for malaria vector control compared with albendazole and no treatment: An open-label randomized controlled trial","authors":"Yvonne Kamau , Mercy Tuwei , Caroline Wanjiku , Kelly Ominde , Mwanajuma Ngama , Jonathan Karisa , Lawrence Babu , Martha Muturi , Mwaganyuma Mwatasa , Jane Adetifa , Charlotte Kern , Urs Duthaler , Felix Hammann , Regina Rabinovich , Carlos Chaccour , Marta Ferreira Maia","doi":"10.1016/j.ijid.2024.107236","DOIUrl":"10.1016/j.ijid.2024.107236","url":null,"abstract":"<div><h3>Objectives</h3><div>When malaria vectors consume ivermectin in a blood meal, their survival probability decreases, potentially reducing malaria transmission during mass drug administrations. However, questions remain regarding the optimal dosing. This study aimed to compare the mosquitocidal effect and pharmacokinetics of two-dose regimens of ivermectin for malaria vector control.</div></div><div><h3>Design</h3><div>We conducted an open-label randomized control trial in Kenya, staggered in blocks with sequential intervention groups and parallel controls. Participants were randomly assigned (2:1:1:1) using computer random-sequence generation, unstratified, with one block of six pharmacokinetics-only participants (single-dose ivermectin) and six blocks of four participants (3:1 intervention vs control), to receive single-dose ivermectin (400 mcg/kg, n = 12), three daily doses (3-day regimen 300 mcg/kg, n = 6), albendazole (400 mg, n = 6), or no treatment (negative control, n = 6). Our primary outcome was <em>Anopheles gambiae</em> survival (time-to-event [days]) after blood feeding up to 10 days after drug administration. We also evaluated pharmacokinetics (peak plasma and capillary blood concentration, areas under the plasma and capillary blood concentration-time curve from time of last administration to time of last observation, time to reach peak plasma and capillary blood concentration, terminal elimination half-life) up to 7 days after treatment.</div></div><div><h3>Results</h3><div>A total of 36 healthy volunteers aged 21-32 years were recruited into the study and followed up to completion, with two participants not attending the visit on day 28. All drug regimens were well-tolerated. Both regimens showed significant mosquitocidal effect in the first 7 days. At 10 days after treatment, the single dose presented superior longevity of effect (adjusted hazard ratio = 3.91; 95% confidence interval = 1.93-7.93; <em>P</em> <0.001) compared with the triple dose (adjusted hazard ratio = 1.79; 95% confidence interval = 0.88-3.62; <em>P</em> = 0.0.11). Albendazole had, overall, no mosquitocidal effect.</div></div><div><h3>Conclusions</h3><div>It is unclear why a single dose led to increased bio-efficacy compared with a triple dose. We recommend trials investigating ivermectin mass drug administrations for malaria control to consider single-dose ivermectin. A single-dose regimen is also expected to present additional operational advantages compared with a 3-day regimen, leading to improved programmatic suitability.</div></div>","PeriodicalId":14006,"journal":{"name":"International Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153976","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}
Pub Date : 2024-09-06DOI: 10.1016/j.ijid.2024.107232
Jaroslav A. Hubacek , Nadezda Capkova , Martin Bobak , Hynek Pikhart
Objectives
COVID-19 caused a global pandemic with millions of deaths. Fat mass and obesity-associated gene (FTO) (alias m6A RNA demethylase) and its functional rs17817449 polymorphism are candidates to influence COVID-19-associated mortality since methylation status of viral nucleic acids is an important factor influencing viral viability.
Methods
We tested a population-based cohort of 5233 subjects (aged 63-87 years in 2020) where 70 persons died from COVID-19 and 394 from other causes during the pandemic period.
Results
The frequency of GG homozygotes was higher among those who died from COVID-19 (34%) than among survivors (19%) or deaths from other causes (20%), P <0.005. After multiple adjustments, GG homozygotes had a higher risk of death from COVID-19 with odds ratio = 2.01 (95% confidence interval; 1.19-3.41, P <0.01) compared with carriers of at least one T allele. The FTO polymorphism was not associated with mortality from other causes.
Conclusions
Our results suggest that FTO variability is a significant predictor of COVID-19-associated mortality in Caucasians.
{"title":"Association between FTO polymorphism and COVID-19 mortality among older adults: A population-based cohort study","authors":"Jaroslav A. Hubacek , Nadezda Capkova , Martin Bobak , Hynek Pikhart","doi":"10.1016/j.ijid.2024.107232","DOIUrl":"10.1016/j.ijid.2024.107232","url":null,"abstract":"<div><h3>Objectives</h3><div>COVID-19 caused a global pandemic with millions of deaths. Fat mass and obesity-associated gene (<em>FTO</em>) (alias m<sup>6</sup>A RNA demethylase) and its functional rs17817449 polymorphism are candidates to influence COVID-19-associated mortality since methylation status of viral nucleic acids is an important factor influencing viral viability.</div></div><div><h3>Methods</h3><div>We tested a population-based cohort of 5233 subjects (aged 63-87 years in 2020) where 70 persons died from COVID-19 and 394 from other causes during the pandemic period.</div></div><div><h3>Results</h3><div>The frequency of GG homozygotes was higher among those who died from COVID-19 (34%) than among survivors (19%) or deaths from other causes (20%), <em>P</em> <0.005. After multiple adjustments, GG homozygotes had a higher risk of death from COVID-19 with odds ratio = 2.01 (95% confidence interval; 1.19-3.41, <em>P</em> <0.01) compared with carriers of at least one T allele. The <em>FTO</em> polymorphism was not associated with mortality from other causes.</div></div><div><h3>Conclusions</h3><div>Our results suggest that <em>FTO</em> variability is a significant predictor of COVID-19-associated mortality in Caucasians.</div></div>","PeriodicalId":14006,"journal":{"name":"International Journal of Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1201971224003035/pdfft?md5=4fa262b746807b7f5d8c637e0d19bd17&pid=1-s2.0-S1201971224003035-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145605","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}
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