Pub Date : 2024-09-10DOI: 10.1101/2024.09.10.24313380
Shihui Jin, Tong Guan, Akira Endo, Gregory Gan, A. Janhavi, Gang Hu, Keisuke Ejima, Jue Tao Lim, Borame L Dickens
BackgroundThe Clade Ib monkeypox virus (MPXV), newly identified in the ongoing 2024 mpox outbreak, can be more transmissible through non-sexual routes compared to the previous Clade IIb strain. With imported cases sporadically reported globally, concerns have emerged about the potential of widespread transmission in the general community after importation events. Border control measures, such as screening and quarantining of arriving travellers, may help mitigate this risk and prevent localized outbreaks in the event of global spread.MethodsWe proposed nine border control strategies and evaluated their effectiveness in reducing importation risk using 10,000 microsimulations of individual infection profiles and PCR testing results under scenarios with varying disease prevalence levels (0.01%, 0.05%, and 0.1%) in the country of origin. ResultsThe proposed border-control measures would reduce missed cases by 40.1% (39.1%-41.0%), 49.8% (48.8%-50.8%), and 58.1% (57.1%-59.0%) for pre-departure, on-arrival, and both tests, respectively. Replacing the on-arrival test with a seven-day quarantine and post-quarantine testing would lower the count to 21.8% (20.9%-22.6%). Quarantine-only strategies showed a linear increase in effectiveness against duration, reaching a 90.4% (89.8%-91.0%) reduction with a 28-day quarantine. Disparities in distributions of missed case counts across strategies would become more pronounced at higher prevalence levels, with stringent approaches like quarantining followed by post-quarantine screening and 28-day quarantine keeping counts below two per 10,000 travellers, even at 0.1% prevalence. ConclusionsWhen disease prevalence in the country of origin is low (0.01%), less restrictive approaches such as single on-arrival testing or a 14-day quarantine can maintain very low imported case counts of one or below. At higher prevalences, seven-day quarantining followed by post-quarantine testing, or 28-day quarantining is required to maintain similar effects. Decision makers will face balancing importation risk management and the negative impacts of such interventions to maintain safe international travel.
{"title":"Border control strategies for reducing importation risk of Clade Ib Mpox","authors":"Shihui Jin, Tong Guan, Akira Endo, Gregory Gan, A. Janhavi, Gang Hu, Keisuke Ejima, Jue Tao Lim, Borame L Dickens","doi":"10.1101/2024.09.10.24313380","DOIUrl":"https://doi.org/10.1101/2024.09.10.24313380","url":null,"abstract":"Background\u0000The Clade Ib monkeypox virus (MPXV), newly identified in the ongoing 2024 mpox outbreak, can be more transmissible through non-sexual routes compared to the previous Clade IIb strain. With imported cases sporadically reported globally, concerns have emerged about the potential of widespread transmission in the general community after importation events. Border control measures, such as screening and quarantining of arriving travellers, may help mitigate this risk and prevent localized outbreaks in the event of global spread.\u0000Methods\u0000We proposed nine border control strategies and evaluated their effectiveness in reducing importation risk using 10,000 microsimulations of individual infection profiles and PCR testing results under scenarios with varying disease prevalence levels (0.01%, 0.05%, and 0.1%) in the country of origin. Results\u0000The proposed border-control measures would reduce missed cases by 40.1% (39.1%-41.0%), 49.8% (48.8%-50.8%), and 58.1% (57.1%-59.0%) for pre-departure, on-arrival, and both tests, respectively. Replacing the on-arrival test with a seven-day quarantine and post-quarantine testing would lower the count to 21.8% (20.9%-22.6%). Quarantine-only strategies showed a linear increase in effectiveness against duration, reaching a 90.4% (89.8%-91.0%) reduction with a 28-day quarantine. Disparities in distributions of missed case counts across strategies would become more pronounced at higher prevalence levels, with stringent approaches like quarantining followed by post-quarantine screening and 28-day quarantine keeping counts below two per 10,000 travellers, even at 0.1% prevalence. Conclusions\u0000When disease prevalence in the country of origin is low (0.01%), less restrictive approaches such as single on-arrival testing or a 14-day quarantine can maintain very low imported case counts of one or below. At higher prevalences, seven-day quarantining followed by post-quarantine testing, or 28-day quarantining is required to maintain similar effects. Decision makers will face balancing importation risk management and the negative impacts of such interventions to maintain safe international travel.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":"65 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142189552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-10DOI: 10.1101/2024.09.10.24313384
Shihui Jin, Gregory Gan, Akira Endo, Kiesha Prem, Rayner Kay Jin Tan, Jue Tao Lim, Keisuke Ejima, Borame L Dickens
BackgroundThe ongoing 2024 mpox outbreak in several African countries, driven by the novel Clade 1b strain, has resulted in imported cases being reported in Sweden and Thailand. The Asia Pacific (APAC) region, with little exposure to previous mpox waves, is particularly vulnerable to local transmission triggered by importation. While this highlights the importance of early preparedness, current knowledge of the virus's transmission dynamics remains too limited to effectively inform policy-making and resource planning. MethodsA compartmental model was constructed to characterise the potential mpox transmission triggered by importation in an APAC city. Outbreaks were simulated under diverse hypothetical scenarios considering transmission mechanisms, different affected subpopulations, levels of disease transmissibility, and importation frequencies. The impacts of various non-pharmaceutical interventions (NPIs) including isolation, and vaccination strategies were projected and compared. FindingsUp to 30% of the population would be infected in the scenario of high sexual and moderate non-sexual transmissibility in the general community, with minimal impact from importation frequency on outbreak size and healthcare burden. The sequential introduction of mandatory home isolation for diagnosed cases, pre-departure screening of international arrivals, and contact tracing were projected to lower the peak outbreak size by 35%, 0.04%, and 1.1%, respectively, while the reduction would be 30% with proper vaccination by prioritising the sexually active group. These measures would significantly decrease disease morbidity and mortality rates, thereby alleviating the disease's pressure on healthcare systems. InterpretationThe potential mpox outbreak in the APAC setting could be alleviated through strong surveillance and timely response from stakeholders. NPIs are recommended over vaccination for outbreak management due to their demonstrated effectiveness and practicability.
{"title":"Modelling the potential spread of Clade Ib MPXV in an Asia Pacific city","authors":"Shihui Jin, Gregory Gan, Akira Endo, Kiesha Prem, Rayner Kay Jin Tan, Jue Tao Lim, Keisuke Ejima, Borame L Dickens","doi":"10.1101/2024.09.10.24313384","DOIUrl":"https://doi.org/10.1101/2024.09.10.24313384","url":null,"abstract":"Background\u0000The ongoing 2024 mpox outbreak in several African countries, driven by the novel Clade 1b strain, has resulted in imported cases being reported in Sweden and Thailand. The Asia Pacific (APAC) region, with little exposure to previous mpox waves, is particularly vulnerable to local transmission triggered by importation. While this highlights the importance of early preparedness, current knowledge of the virus's transmission dynamics remains too limited to effectively inform policy-making and resource planning. Methods\u0000A compartmental model was constructed to characterise the potential mpox transmission triggered by importation in an APAC city. Outbreaks were simulated under diverse hypothetical scenarios considering transmission mechanisms, different affected subpopulations, levels of disease transmissibility, and importation frequencies. The impacts of various non-pharmaceutical interventions (NPIs) including isolation, and vaccination strategies were projected and compared. Findings\u0000Up to 30% of the population would be infected in the scenario of high sexual and moderate non-sexual transmissibility in the general community, with minimal impact from importation frequency on outbreak size and healthcare burden. The sequential introduction of mandatory home isolation for diagnosed cases, pre-departure screening of international arrivals, and contact tracing were projected to lower the peak outbreak size by 35%, 0.04%, and 1.1%, respectively, while the reduction would be 30% with proper vaccination by prioritising the sexually active group. These measures would significantly decrease disease morbidity and mortality rates, thereby alleviating the disease's pressure on healthcare systems. Interpretation\u0000The potential mpox outbreak in the APAC setting could be alleviated through strong surveillance and timely response from stakeholders. NPIs are recommended over vaccination for outbreak management due to their demonstrated effectiveness and practicability.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142189576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-10DOI: 10.1101/2024.09.10.24313149
Mengou Zhu, Chiagozie O Pickens, Nikolay S Markov, Anna E Pawlowski, Mengjia Kang, Luke V Rasmussen, James M Walter, Nandita R Nadig, Benjamin D Singer, Richard G Wunderink, Catherine A Gao, The NU SCRIPT Investigators
Background: Antibiotic stewardship in critically ill pneumonia patients is crucial yet challenging, partly due to the limited diagnostic yield of noninvasive infectious tests. In this study, we report an antibiotic prescription pattern informed by bronchoalveolar lavage (BAL) results, where clinicians de-escalate antibiotics based on the combination of quantitative cultures and multiplex PCR rapid diagnostic tests. Methods: We analyzed data from SCRIPT, a single-center prospective cohort study of mechanically ventilated patients who underwent a BAL for suspected pneumonia. We used the novel Narrow Antibiotic Therapy (NAT) score to quantify day-by-day antibiotic prescription pattern for each suspected pneumonia episode etiology (bacterial, viral, mixed bacterial/viral, microbiology-negative, and non-pneumonia control). We also analyzed and compared clinical outcomes for each pneumonia etiology, including unfavorable outcomes (a composite of in-hospital mortality, discharge to hospice, or requiring lung transplantation during hospitalization), duration of ICU stay, and duration of intubation. Clinical outcomes were compared with the Mann-Whitney U test and Fisher's exact test. Results: We included 686 patients with 927 pneumonia episodes. NAT score analysis indicated that an antibiotic de-escalation pattern was evident in all pneumonia etiologies except resistant bacterial pneumonia. Microbiology-negative pneumonia was treated similarly to susceptible bacterial pneumonia in terms of antibiotic spectrum. Over a quarter of the time in viral pneumonia episodes, antibiotics were completely discontinued. Unfavorable outcomes were comparable across all pneumonia etiologies. Patients with viral and mixed bacterial/viral pneumonia had longer durations of ICU stay and intubation.Conclusions: BAL quantitative cultures and multiplex PCR rapid diagnostic tests resulted in prompt antibiotic de-escalation in critically ill pneumonia patients. There was no evidence of increased incidence of unfavorable outcomes.
{"title":"Antibiotic De-escalation Patterns and Outcomes in Critically Ill Patients with Suspected Pneumonia as Informed by Bronchoalveolar Lavage Results","authors":"Mengou Zhu, Chiagozie O Pickens, Nikolay S Markov, Anna E Pawlowski, Mengjia Kang, Luke V Rasmussen, James M Walter, Nandita R Nadig, Benjamin D Singer, Richard G Wunderink, Catherine A Gao, The NU SCRIPT Investigators","doi":"10.1101/2024.09.10.24313149","DOIUrl":"https://doi.org/10.1101/2024.09.10.24313149","url":null,"abstract":"Background: Antibiotic stewardship in critically ill pneumonia patients is crucial yet challenging, partly due to the limited diagnostic yield of noninvasive infectious tests. In this study, we report an antibiotic prescription pattern informed by bronchoalveolar lavage (BAL) results, where clinicians de-escalate antibiotics based on the combination of quantitative cultures and multiplex PCR rapid diagnostic tests. Methods: We analyzed data from SCRIPT, a single-center prospective cohort study of mechanically ventilated patients who underwent a BAL for suspected pneumonia. We used the novel Narrow Antibiotic Therapy (NAT) score to quantify day-by-day antibiotic prescription pattern for each suspected pneumonia episode etiology (bacterial, viral, mixed bacterial/viral, microbiology-negative, and non-pneumonia control). We also analyzed and compared clinical outcomes for each pneumonia etiology, including unfavorable outcomes (a composite of in-hospital mortality, discharge to hospice, or requiring lung transplantation during hospitalization), duration of ICU stay, and duration of intubation. Clinical outcomes were compared with the Mann-Whitney U test and Fisher's exact test. Results: We included 686 patients with 927 pneumonia episodes. NAT score analysis indicated that an antibiotic de-escalation pattern was evident in all pneumonia etiologies except resistant bacterial pneumonia. Microbiology-negative pneumonia was treated similarly to susceptible bacterial pneumonia in terms of antibiotic spectrum. Over a quarter of the time in viral pneumonia episodes, antibiotics were completely discontinued. Unfavorable outcomes were comparable across all pneumonia etiologies. Patients with viral and mixed bacterial/viral pneumonia had longer durations of ICU stay and intubation.\u0000Conclusions: BAL quantitative cultures and multiplex PCR rapid diagnostic tests resulted in prompt antibiotic de-escalation in critically ill pneumonia patients. There was no evidence of increased incidence of unfavorable outcomes.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142189554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-10DOI: 10.1101/2024.09.09.24313370
Jianyu Lai, P. Jacob Bueno de Mesquita, Filbert Hong, Tianzhou Ma, Benjamin J. Cowling, Donald K. Milton
Nasally inoculated influenza cases reported milder symptoms and shed lower viral RNA load in exhaled breath aerosols (EBA) than people with classic influenza-like illness including fever, in a previous study. Whether nasally inoculated influenza is representative of mild natural influenza infection, the majority of natural infections, is unknown. Here, we extend our previous analyses to include a broader range of community-acquired influenza cases. Previously, we reported on two groups: (A) volunteers intranasally inoculated with a dose of 5.5 log10TCID50 of influenza A/Wisconsin/67/2005 (H3N2) and (B) cases with cough and sore throat plus fever or a positive rapid antigen test recruited on a college campus in the same year (2013). Here we added two additional groups from a later study: (C) cases from a 2017-2019 surveillance cohort of college dormitory residents and their contacts, and (D) cases recruited from a university health center in 2019. All cases had an influenza A(H3) infection. Using a Gesundheit-II sampler, we collected 30-minute EBA samples. Community-acquired cases from the surveillance cohort (C) shed more EBA viral RNA and were more symptomatic than the nasally inoculated cases (A) but shed less viral RNA than the natural cases that were selected for symptoms (B) in 2013, but not (D) recruited in 2019. Despite sharing a similar symptomatic profile with the 2013 selected natural cases (B), the 2019 community-acquired cases (D) recruited post-infection showed a lower fine aerosol viral RNA load. Nasal inoculation of influenza virus did not reproduce EBA viral RNA shedding or symptoms observed in mild natural infection. Circulating strains of influenza A(H3) may differ, year-to-year in the extent to which symptomatic cases shed virus into fine aerosols. New models, including possibly aerosol inoculation, are needed to study viral aerosol shedding from the human respiratory tract.
{"title":"Influenza A (H3) viral aerosol shedding in nasally inoculated and naturally infected cases","authors":"Jianyu Lai, P. Jacob Bueno de Mesquita, Filbert Hong, Tianzhou Ma, Benjamin J. Cowling, Donald K. Milton","doi":"10.1101/2024.09.09.24313370","DOIUrl":"https://doi.org/10.1101/2024.09.09.24313370","url":null,"abstract":"Nasally inoculated influenza cases reported milder symptoms and shed lower viral RNA load in exhaled breath aerosols (EBA) than people with classic influenza-like illness including fever, in a previous study. Whether nasally inoculated influenza is representative of mild natural influenza infection, the majority of natural infections, is unknown. Here, we extend our previous analyses to include a broader range of community-acquired influenza cases. Previously, we reported on two groups: (A) volunteers intranasally inoculated with a dose of 5.5 log10TCID50 of influenza A/Wisconsin/67/2005 (H3N2) and (B) cases with cough and sore throat plus fever or a positive rapid antigen test recruited on a college campus in the same year (2013). Here we added two additional groups from a later study: (C) cases from a 2017-2019 surveillance cohort of college dormitory residents and their contacts, and (D) cases recruited from a university health center in 2019. All cases had an influenza A(H3) infection. Using a Gesundheit-II sampler, we collected 30-minute EBA samples. Community-acquired cases from the surveillance cohort (C) shed more EBA viral RNA and were more symptomatic than the nasally inoculated cases (A) but shed less viral RNA than the natural cases that were selected for symptoms (B) in 2013, but not (D) recruited in 2019. Despite sharing a similar symptomatic profile with the 2013 selected natural cases (B), the 2019 community-acquired cases (D) recruited post-infection showed a lower fine aerosol viral RNA load. Nasal inoculation of influenza virus did not reproduce EBA viral RNA shedding or symptoms observed in mild natural infection. Circulating strains of influenza A(H3) may differ, year-to-year in the extent to which symptomatic cases shed virus into fine aerosols. New models, including possibly aerosol inoculation, are needed to study viral aerosol shedding from the human respiratory tract.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142189553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-10DOI: 10.1101/2024.09.10.24313404
Eva Kozanli, Wanda Han, Tara Smit, Jordy de Bakker, Mansoer Elahi, Ryanne Jaarsma, Gesa Carstens, Albert Jan van Hoek, Dirk Eggink
BackgroundRapid Diagnostic Tests (RDTs) have been pivotal in the diagnostics for SARS-CoV-2 and policies surrounding self-isolation. When self-testing policies are in place a decreased sensitivity of the virus to RDTs can give benefits for viral spread. However, to monitor for reduced sensitivity of RDTs we rely on the collection of SARS-CoV-2 positive samples from RDT negative patients. Infectieradar, a national participatory surveillance that registers influenza-like symptoms is used as a framework to study false-negative RDT results due to emergence of new virus variants. MethodsParticipants report weekly on RDT use and symptoms linked to Acute Respiratory Illness (ARI). Each week, all RDT positive and a sample of 200 among RDT negative but symptomatic participants were invited to send in nose throat swabs (NTS). SARS-CoV-2 Ct-values are determined using RT-PCR on NTS samples for RDT positive and RDT (false) negative participants and compared. Sequencing is performed on all eligible samples for phylogenetic analysis of the SARS-CoV-2 nucleocapsid protein and the whole genome sequence. NTS samples of participants with discordant RT-PCR and RDT results are also analyzed using RDTs by professionals in the laboratory. ResultsBetween October 2022 and October 2023, our study had 16,893 participants and we collected 1,757 self-test-positive/NTS PCR positive samples and 359 self-test-negative/NTS PCR positive samples (RDT-/PCR+). These participants were asked to take a SARS-CoV-2 RDT upon symptoms. Within SARS-CoV-2 PCR positive participants, we did not find characteristics that differ in SARS-CoV-2 RDT negative versus positive participants. There were no associations with specific changes in the N protein nor did our phylogenetic analysis show clustering of RDT negative samples. ConclusionEvaluating brand-specific RDT performance in Dutch population and false-negative RDT analyses, led to no evidence for SARS-CoV-2 evolution affecting RDT sensitivity. The participatory surveillance program Infectieradar is a powerful tool for our national surveillance on acute respiratory illnesses, as well as for research purposes. Since this framework offered both self-testing and the gold standard of PCR testing results.
{"title":"Dutch participatory surveillance framework for evaluating evolutionary changes on SARS-CoV-2 affecting Rapid Diagnostic Test sensitivity in 2022 - 2023.","authors":"Eva Kozanli, Wanda Han, Tara Smit, Jordy de Bakker, Mansoer Elahi, Ryanne Jaarsma, Gesa Carstens, Albert Jan van Hoek, Dirk Eggink","doi":"10.1101/2024.09.10.24313404","DOIUrl":"https://doi.org/10.1101/2024.09.10.24313404","url":null,"abstract":"Background\u0000Rapid Diagnostic Tests (RDTs) have been pivotal in the diagnostics for SARS-CoV-2 and policies surrounding self-isolation. When self-testing policies are in place a decreased sensitivity of the virus to RDTs can give benefits for viral spread. However, to monitor for reduced sensitivity of RDTs we rely on the collection of SARS-CoV-2 positive samples from RDT negative patients. Infectieradar, a national participatory surveillance that registers influenza-like symptoms is used as a framework to study false-negative RDT results due to emergence of new virus variants. Methods\u0000Participants report weekly on RDT use and symptoms linked to Acute Respiratory Illness (ARI). Each week, all RDT positive and a sample of 200 among RDT negative but symptomatic participants were invited to send in nose throat swabs (NTS). SARS-CoV-2 Ct-values are determined using RT-PCR on NTS samples for RDT positive and RDT (false) negative participants and compared. Sequencing is performed on all eligible samples for phylogenetic analysis of the SARS-CoV-2 nucleocapsid protein and the whole genome sequence. NTS samples of participants with discordant RT-PCR and RDT results are also analyzed using RDTs by professionals in the laboratory. Results\u0000Between October 2022 and October 2023, our study had 16,893 participants and we collected 1,757 self-test-positive/NTS PCR positive samples and 359 self-test-negative/NTS PCR positive samples (RDT-/PCR+). These participants were asked to take a SARS-CoV-2 RDT upon symptoms. Within SARS-CoV-2 PCR positive participants, we did not find characteristics that differ in SARS-CoV-2 RDT negative versus positive participants. There were no associations with specific changes in the N protein nor did our phylogenetic analysis show clustering of RDT negative samples. Conclusion\u0000Evaluating brand-specific RDT performance in Dutch population and false-negative RDT analyses, led to no evidence for SARS-CoV-2 evolution affecting RDT sensitivity. The participatory surveillance program Infectieradar is a powerful tool for our national surveillance on acute respiratory illnesses, as well as for research purposes. Since this framework offered both self-testing and the gold standard of PCR testing results.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":"70 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142189575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-09DOI: 10.1101/2024.09.08.24313270
James M Crawford, Lynne Penberthy, Ligia A Pinto, Keri N Althoff, Magdalene M Assimon, Oren Cohen, Laura Gillim, Tracy L Hammonds, Shilpa Kapur, Harvey W Kaufman, David Kwasny, Jean W Liew, William A Meyer, Shannon L Reynolds, Cheryl B Schleicher, Suki Subbiah, Catherine Theruviparampil, Zachary S Wallace, Jeremy L Warner, Nicole Yoon, Yonah C Ziemba
Background: We created a United States-based real-world data resource to better understand the continued impact of the COVID-19 pandemic on immunocompromised patients, who are typically under-represented in prospective studies and clinical trials. Methods: The COVID-19 Real World Data infrastructure (CRWDi) was created by linking and harmonizing deidentified HealthVerity medical and pharmacy claims data from December 1, 2018 to December 31, 2023, with SARS-CoV-2 virologic and serologic laboratory data from major commercial laboratories and Northwell Health; COVID-19 vaccination data; and for patients with cancer, 2010 to 2021 National Cancer Institute Surveillance, Epidemiology, and End Results registry data. Results: The CRWDi dataset contains data on 5.2 million people. Four populations were included in the dataset: (1) patients with cancer (n=1,294,022); (2) patients with rheumatic conditions receiving pharmacotherapy (n=1,636,940); (3) non-cancer solid organ (n=249,797) and hematopoietic stem cell (n=30,172) transplant recipients; and (4) people from the general population including adults (>18 years of age; n=1,790,162) and pediatric patients (<18 years of age; n=198,907). Conclusions: We have created a complex real-world data system to address unanswered questions that have arisen during the COVID-19 pandemic. Further, by making the data broadly and freely available to academic researchers from the United States, the CRWDi real-world data system represents an important complement to existing consortia studies and clinical trials that have emerged during the healthcare crisis, and is readily reproducible for future purposing.
{"title":"COVID-19 real world data infrastructure: A big data resource for study of the impact of COVID-19 in patient populations with immunocompromising conditions","authors":"James M Crawford, Lynne Penberthy, Ligia A Pinto, Keri N Althoff, Magdalene M Assimon, Oren Cohen, Laura Gillim, Tracy L Hammonds, Shilpa Kapur, Harvey W Kaufman, David Kwasny, Jean W Liew, William A Meyer, Shannon L Reynolds, Cheryl B Schleicher, Suki Subbiah, Catherine Theruviparampil, Zachary S Wallace, Jeremy L Warner, Nicole Yoon, Yonah C Ziemba","doi":"10.1101/2024.09.08.24313270","DOIUrl":"https://doi.org/10.1101/2024.09.08.24313270","url":null,"abstract":"Background: We created a United States-based real-world data resource to better understand the continued impact of the COVID-19 pandemic on immunocompromised patients, who are typically under-represented in prospective studies and clinical trials. Methods: The COVID-19 Real World Data infrastructure (CRWDi) was created by linking and harmonizing deidentified HealthVerity medical and pharmacy claims data from December 1, 2018 to December 31, 2023, with SARS-CoV-2 virologic and serologic laboratory data from major commercial laboratories and Northwell Health; COVID-19 vaccination data; and for patients with cancer, 2010 to 2021 National Cancer Institute Surveillance, Epidemiology, and End Results registry data. Results: The CRWDi dataset contains data on 5.2 million people. Four populations were included in the dataset: (1) patients with cancer (n=1,294,022); (2) patients with rheumatic conditions receiving pharmacotherapy (n=1,636,940); (3) non-cancer solid organ (n=249,797) and hematopoietic stem cell (n=30,172) transplant recipients; and (4) people from the general population including adults (>18 years of age; n=1,790,162) and pediatric patients (<18 years of age; n=198,907). Conclusions: We have created a complex real-world data system to address unanswered questions that have arisen during the COVID-19 pandemic. Further, by making the data broadly and freely available to academic researchers from the United States, the CRWDi real-world data system represents an important complement to existing consortia studies and clinical trials that have emerged during the healthcare crisis, and is readily reproducible for future purposing.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":"394 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142189580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-09DOI: 10.1101/2024.09.09.24313305
Ivan Gentile, Riccardo Scotto, Maria Michela Scirocco, Francesco Di Brizzi, Federica Cuccurullo, Maria Silvitelli, Luigi Ametrano, Francesco Antimo Alfe', Daria Pietroluongo, Irene Irace, Mariarosaria Chiariello, Noemi De Felice, Simone Severino, Giulio Viceconte, Nicola Schiano Moriello, Alberto Enrico Maraolo, Antonio Riccardo Buonomo, Agnese Giaccone, Federico II COVID Team
IntroductionMolnupiravir (MNP) is an orally administered prodrug which prevents disease progression in patients at high risk for severe COVID-19. We conducted a real-life case-control study on a cohort of outpatients, with Omicron SARS-CoV-2 infection to assess the effectiveness of MNP in reducing the occurrence of hospital admission, admission in intensive care unit (ICU) and death at day 28.Materials and methodsCases were enrolled among SARS-CoV-2 positive subjects that sought medical care during the first five days of symptoms from January 1st, 2022, to December 31st, 2022, and received MNP. Control participants were selected from a regional database among those who tested positive during the study period and did not receive antiviral treatment for SARS-CoV-2. Results1382 patients were included (cases: 146, controls: 1236). Vaccinated patients showed lower risk of mortality and composite outcome (at least one among hospital admission, admission in ICU and all-cause death) compared to unvaccinated ones (0.6% vs 7.8%, p<0.001 and 2% vs 7.8%, p=0.001 respectively). After full-matching propensity score, MNP-treated subjects showed a lower incidence of composite outcome, while no effect was observed on the single outcomes. In the subgroup analysis according to the vaccination status, MNP proved effective in preventing all the outcomes among unvaccinated patients, while showed to reduce the risk of ICU admission both in vaccinated and unvaccinated patients.ConclusionsTreatment with MNP proved effective in reducing the risk of composite outcome among outpatients with SARS-CoV-2 infection. The beneficial effect of MNP treatment in reducing progression is more pronounced in unvaccinated patients.
{"title":"Efficacy of Molnupiravir in reducing the risk of severe outcome in patients with SARS-CoV-2 infection: a real-life full-matched case-control study (SAVALO Study).","authors":"Ivan Gentile, Riccardo Scotto, Maria Michela Scirocco, Francesco Di Brizzi, Federica Cuccurullo, Maria Silvitelli, Luigi Ametrano, Francesco Antimo Alfe', Daria Pietroluongo, Irene Irace, Mariarosaria Chiariello, Noemi De Felice, Simone Severino, Giulio Viceconte, Nicola Schiano Moriello, Alberto Enrico Maraolo, Antonio Riccardo Buonomo, Agnese Giaccone, Federico II COVID Team","doi":"10.1101/2024.09.09.24313305","DOIUrl":"https://doi.org/10.1101/2024.09.09.24313305","url":null,"abstract":"Introduction\u0000Molnupiravir (MNP) is an orally administered prodrug which prevents disease progression in patients at high risk for severe COVID-19. We conducted a real-life case-control study on a cohort of outpatients, with Omicron SARS-CoV-2 infection to assess the effectiveness of MNP in reducing the occurrence of hospital admission, admission in intensive care unit (ICU) and death at day 28.\u0000Materials and methods\u0000Cases were enrolled among SARS-CoV-2 positive subjects that sought medical care during the first five days of symptoms from January 1st, 2022, to December 31st, 2022, and received MNP. Control participants were selected from a regional database among those who tested positive during the study period and did not receive antiviral treatment for SARS-CoV-2. Results\u00001382 patients were included (cases: 146, controls: 1236). Vaccinated patients showed lower risk of mortality and composite outcome (at least one among hospital admission, admission in ICU and all-cause death) compared to unvaccinated ones (0.6% vs 7.8%, p<0.001 and 2% vs 7.8%, p=0.001 respectively). After full-matching propensity score, MNP-treated subjects showed a lower incidence of composite outcome, while no effect was observed on the single outcomes. In the subgroup analysis according to the vaccination status, MNP proved effective in preventing all the outcomes among unvaccinated patients, while showed to reduce the risk of ICU admission both in vaccinated and unvaccinated patients.\u0000Conclusions\u0000Treatment with MNP proved effective in reducing the risk of composite outcome among outpatients with SARS-CoV-2 infection. The beneficial effect of MNP treatment in reducing progression is more pronounced in unvaccinated patients.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142189578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-09DOI: 10.1101/2024.09.07.24313132
Zachary R Popkin-Hall, Kelly Carey-Ewend, Farhang Aghakhanian, Eniyou C Oriero, Misago D Seth, Melchior M Kashamuka, Billy Ngasala, Innocent M Ali, Eric S Mukomena, Celine I Mandara, Oksana Kharabora, Rachel Sendor, Alfred Simkin, Alfred Amambua-Ngwa, Antoinette Tshefu, Abebe A Fola, Jeffrey A Bailey, Deus S Ishengoma, Jonathan B Parr, Jessica T Lin, Jonathan J Juliano
Plasmodium malariae is geographically widespread but neglected and may become more prevalent as P. falciparum declines. We completed the largest genomic study of African P. malariae to-date by performing hybrid capture and sequencing of 77 isolates from Cameroon (n=7), the Democratic Republic of the Congo (n=16), Nigeria (n=4), and Tanzania (n=50) collected between 2015 and 2021. There is no evidence of geographic population structure. Nucleotide diversity was significantly lower than in co-localized P. falciparum isolates, while linkage disequilibrium was significantly higher. Genome-wide selection scans identified no erythrocyte invasion ligands or antimalarial resistance orthologs as top hits; however, targeted analyses of these loci revealed evidence of selective sweeps around four erythrocyte invasion ligands and six antimalarial resistance orthologs. Demographic inference modeling suggests that African P. malariae is recovering from a bottleneck. Altogether, these results suggest that P. malariae is genomically atypical among human Plasmodium spp. and panmictic in Africa.
{"title":"Population Genomics of Plasmodium malariae from Four African Countries","authors":"Zachary R Popkin-Hall, Kelly Carey-Ewend, Farhang Aghakhanian, Eniyou C Oriero, Misago D Seth, Melchior M Kashamuka, Billy Ngasala, Innocent M Ali, Eric S Mukomena, Celine I Mandara, Oksana Kharabora, Rachel Sendor, Alfred Simkin, Alfred Amambua-Ngwa, Antoinette Tshefu, Abebe A Fola, Jeffrey A Bailey, Deus S Ishengoma, Jonathan B Parr, Jessica T Lin, Jonathan J Juliano","doi":"10.1101/2024.09.07.24313132","DOIUrl":"https://doi.org/10.1101/2024.09.07.24313132","url":null,"abstract":"Plasmodium malariae is geographically widespread but neglected and may become more prevalent as P. falciparum declines. We completed the largest genomic study of African P. malariae to-date by performing hybrid capture and sequencing of 77 isolates from Cameroon (n=7), the Democratic Republic of the Congo (n=16), Nigeria (n=4), and Tanzania (n=50) collected between 2015 and 2021. There is no evidence of geographic population structure. Nucleotide diversity was significantly lower than in co-localized P. falciparum isolates, while linkage disequilibrium was significantly higher. Genome-wide selection scans identified no erythrocyte invasion ligands or antimalarial resistance orthologs as top hits; however, targeted analyses of these loci revealed evidence of selective sweeps around four erythrocyte invasion ligands and six antimalarial resistance orthologs. Demographic inference modeling suggests that African P. malariae is recovering from a bottleneck. Altogether, these results suggest that P. malariae is genomically atypical among human Plasmodium spp. and panmictic in Africa.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":"65 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142189579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-08DOI: 10.1101/2024.09.04.24312892
Jaime Usuga, Daniel Limonta, Laura S. Perez-Restrepo, Karl A. Ciuoderis, Isabel Moreno, Angela Arevalo, Vanessa Vargas, Michael G. Berg, Gavin A. Cloherty, Juan P. Hernandez-Ortiz, Jorge E. Osorio
In early 2024, explosive outbreaks of Oropouche virus (OROV) linked to a novel viral lineage were documented in the Brazilian Amazon. Here, we report the introduction of this emerging orthobunyavirus into Colombia and its co-circulation with another OROV lineage. This investigation highlights the complex arbovirus dynamics in South America.
{"title":"Co-circulation of two lineages of Oropouche virus in the Amazon basin, Colombia, 2024","authors":"Jaime Usuga, Daniel Limonta, Laura S. Perez-Restrepo, Karl A. Ciuoderis, Isabel Moreno, Angela Arevalo, Vanessa Vargas, Michael G. Berg, Gavin A. Cloherty, Juan P. Hernandez-Ortiz, Jorge E. Osorio","doi":"10.1101/2024.09.04.24312892","DOIUrl":"https://doi.org/10.1101/2024.09.04.24312892","url":null,"abstract":"In early 2024, explosive outbreaks of Oropouche virus (OROV) linked to a novel viral lineage were documented in the Brazilian Amazon. Here, we report the introduction of this emerging orthobunyavirus into Colombia and its co-circulation with another OROV lineage. This investigation highlights the complex arbovirus dynamics in South America.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":"11 2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142189601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-06DOI: 10.1101/2024.09.06.24313176
Prince Baffour Tonto, Mouhamad Sy, Ibrahima Mbaye Ndiaye, Mariama Toure, Amy Gaye, Mariama Aidara, Amadou Moctar Mbaye, Abdoulaye Kane Dia, Mamadou Alpha Diallo, Jules Francois Gomis, Mamadou Samba Yade, Younous Diedhiou, Baba Dieye, Khadim Diongue, Mame Cheikh Seck, Aida S. Badiane, Bobby Brooke Herrera, Daouda Ndiaye
Background Arthritogenic alphaviruses such as chikungunya (CHIKV) and o’nyong-nyong (ONNV) viruses have shown capacity to cause widespread epidemics, with recurrent and sporadic outbreaks occurring throughout sub-Saharan Africa.
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