Pub Date : 2024-09-18DOI: 10.1101/2024.09.17.24313609
Valentina Mazzotta, Pierluca Piselli, Alessandro Cozzi Lepri, Giulia Matusali, Eleonora Cimini, Rozenn Esvan, Francesca Colavita, Roberta Gagliardini, Stefania Notari, Alessandra Oliva, Silvia Meschi, Rita Casetti, Giulia Micheli, Licia Bordi, Alessandro Giacinta, Germana Grassi, Saba Gebremeskel Tekle, Claudia Cimaglia, Jessica Paulicelli, Alessandro Caioli, Paola Galli', Giulia Del Duca, Miriam Lichtner, Loredana Sarmati, Enrica Tamburrini, Claudio Mastroianni, Alessandra Latini, Paolo Faccendini, Carla Fontana, Emanuele Nicastri, Andrea Siddu, Alessandra Barca, Francesco Vaia, Enrico Girardi, Fabrizio Maggi, Andrea Antinori
The recent resurgence of Mpox in central Africa has been declared again a Public Health Emergency of International Concern (PHEIC) requiring coordinated international responses. Vaccination is a priority to expand protection and enhance control strategies, but the vaccine's need exceeds the currently available doses. Intradermal administration of one-fifth of the standard Modified-Vaccinia-Ankara (MVA-BN) dose was temporarily authorized during the 2022 PHEIC. Studies conducted before 2022 provided evidence about the humoral response against the Vaccinia virus (VACV) after vaccination but not against the Mpox virus (MPXV). Moreover, no data are available on the T-cell response elicited by MVA-BN administered subcutaneously or intradermally. Here, we compare the two vaccine administration routes according to reactogenicity and immunogenicity based on data from 943 vaccine recipients during the 2022 vaccination campaign in Rome, Italy. We found that the intradermal route elicited slightly higher titers of MPXV-specific IgG and nAbs than the subcutaneous one. At the same time, no differences in cellular response were detected. MVA-BN was globally well tolerated despite higher reactogenicity for the intradermal than the subcutaneous route, especially for the reactions at the local injection site. The intradermal dose-sparing strategy was proven safe and immunogenic and would make vaccination available to more people.
{"title":"Reactogenicity and immunogenicity against MPXV of the intradermal administration of Modified V Vaccinia Ankara compared to the standard subcutaneous route.","authors":"Valentina Mazzotta, Pierluca Piselli, Alessandro Cozzi Lepri, Giulia Matusali, Eleonora Cimini, Rozenn Esvan, Francesca Colavita, Roberta Gagliardini, Stefania Notari, Alessandra Oliva, Silvia Meschi, Rita Casetti, Giulia Micheli, Licia Bordi, Alessandro Giacinta, Germana Grassi, Saba Gebremeskel Tekle, Claudia Cimaglia, Jessica Paulicelli, Alessandro Caioli, Paola Galli', Giulia Del Duca, Miriam Lichtner, Loredana Sarmati, Enrica Tamburrini, Claudio Mastroianni, Alessandra Latini, Paolo Faccendini, Carla Fontana, Emanuele Nicastri, Andrea Siddu, Alessandra Barca, Francesco Vaia, Enrico Girardi, Fabrizio Maggi, Andrea Antinori","doi":"10.1101/2024.09.17.24313609","DOIUrl":"https://doi.org/10.1101/2024.09.17.24313609","url":null,"abstract":"The recent resurgence of Mpox in central Africa has been declared again a Public Health Emergency of International Concern (PHEIC) requiring coordinated international responses. Vaccination is a priority to expand protection and enhance control strategies, but the vaccine's need exceeds the currently available doses. Intradermal administration of one-fifth of the standard Modified-Vaccinia-Ankara (MVA-BN) dose was temporarily authorized during the 2022 PHEIC. Studies conducted before 2022 provided evidence about the humoral response against the Vaccinia virus (VACV) after vaccination but not against the Mpox virus (MPXV). Moreover, no data are available on the T-cell response elicited by MVA-BN administered subcutaneously or intradermally. Here, we compare the two vaccine administration routes according to reactogenicity and immunogenicity based on data from 943 vaccine recipients during the 2022 vaccination campaign in Rome, Italy. We found that the intradermal route elicited slightly higher titers of MPXV-specific IgG and nAbs than the subcutaneous one. At the same time, no differences in cellular response were detected. MVA-BN was globally well tolerated despite higher reactogenicity for the intradermal than the subcutaneous route, especially for the reactions at the local injection site. The intradermal dose-sparing strategy was proven safe and immunogenic and would make vaccination available to more people.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265947","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 : 2024-09-17DOI: 10.1101/2024.09.16.24310433
Seven J.S. Aghdassi, Suzanne D. van der Werff, Gaud Catho, Manon Brekelmans, Luis A. Peña Diaz, Niccolò Buetti, Ferenc D. Rüther, Daniel Dinis Teixeira, Daniel Sjöholm, Pontus Nauclér, Michael Behnke, Maaike S.M. van Mourik, on behalf of the PRAISE-HOB working group
Background: Conventional manual surveillance of healthcare-associated infections is labour-intensive and therefore often restricted to areas with high-risk patients. Fully automated surveillance of hospital-onset bacteraemia and fungaemia (HOB) may facilitate hospital-wide surveillance. Aim: To develop an algorithm and minimal dataset (MDS) required for automated surveillance of HOB and apply it to real-life routine data in four European hospitals. Methods: Through consensus discussion a HOB definition with MDS suitable for automated surveillance was developed and applied in a retrospective multicentre observational study including all admitted adult patients (2018-2022). HOB was defined as a positive blood culture with a recognised pathogen two or more days after hospital admission. For common commensals, two blood cultures with the same commensal within two days were required. Annual HOB rates were calculated per 1,000 patient days for the hospital and for intensive care units (ICU) and non-ICU. Results: HOB rates were comparable between the four hospitals (1.0 to 2.2 per 1,000 patient days). HOB rates were substantially higher in ICU than non-ICU across the four hospitals, and HOB with common commensals accounted for 14.8-28.2% of all HOB. HOB rates per 1,000 patient days were rather consistent over time, but were higher in 2020 and 2021. HOB caused by Staphylococcus aureus accounted for 8.4-16.0% of all HOB. Conclusion: Automated HOB surveillance using a common definition was feasible and reproducible across four European hospitals. Future studies should investigate clinical relevance and preventability of HOB, and focus on strategies to make the automated HOB metric an actionable infection control tool.
{"title":"Hospital-onset bacteraemia and fungaemia as a novel automated surveillance indicator: results from four European university hospitals","authors":"Seven J.S. Aghdassi, Suzanne D. van der Werff, Gaud Catho, Manon Brekelmans, Luis A. Peña Diaz, Niccolò Buetti, Ferenc D. Rüther, Daniel Dinis Teixeira, Daniel Sjöholm, Pontus Nauclér, Michael Behnke, Maaike S.M. van Mourik, on behalf of the PRAISE-HOB working group","doi":"10.1101/2024.09.16.24310433","DOIUrl":"https://doi.org/10.1101/2024.09.16.24310433","url":null,"abstract":"Background: Conventional manual surveillance of healthcare-associated infections is labour-intensive and therefore often restricted to areas with high-risk patients. Fully automated surveillance of hospital-onset bacteraemia and fungaemia (HOB) may facilitate hospital-wide surveillance.\u0000Aim: To develop an algorithm and minimal dataset (MDS) required for automated surveillance of HOB and apply it to real-life routine data in four European hospitals. Methods: Through consensus discussion a HOB definition with MDS suitable for automated surveillance was developed and applied in a retrospective multicentre observational study including all admitted adult patients (2018-2022). HOB was defined as a positive blood culture with a recognised pathogen two or more days after hospital admission. For common commensals, two blood cultures with the same commensal within two days were required. Annual HOB rates were calculated per 1,000 patient days for the hospital and for intensive care units (ICU) and non-ICU. Results: HOB rates were comparable between the four hospitals (1.0 to 2.2 per 1,000 patient days). HOB rates were substantially higher in ICU than non-ICU across the four hospitals, and HOB with common commensals accounted for 14.8-28.2% of all HOB. HOB rates per 1,000 patient days were rather consistent over time, but were higher in 2020 and 2021. HOB caused by Staphylococcus aureus accounted for 8.4-16.0% of all HOB.\u0000Conclusion: Automated HOB surveillance using a common definition was feasible and reproducible across four European hospitals. Future studies should investigate clinical relevance and preventability of HOB, and focus on strategies to make the automated HOB metric an actionable infection control tool.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265949","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 : 2024-09-17DOI: 10.1101/2024.09.15.24313552
Elena Perez Anton, Annick Dujeancourt-Henry, Brice Rotureau, Lucy Glover
The WHO aims to eliminate the gambiense form of human African trypanosomiasis (HAT) by 2030. With the decrease of new reported cases, maintaining an efficient epidemiological surveillance is essential, including the emergence of drug-resistant strains. We have developed new highly specific diagnostic tools using Specific High-Sensitivity Reporter Enzymatic UnLOCKing (SHERLOCK) technology for monitoring the presence of drug-resistant genotypes that (1) are already circulating, such as the AQP2/3(814) chimera providing resistance to pentamidine and melarsoprol, or (2) could emerge, such as TbCPSF3 (N232H), associated to acoziborole resistance in lab conditions. The melarsoprol - pentamidine AQP2/3(814) SHERLOCK assay detected RNA from both cultured parasites and field isolated strains from gHAT patients in relapse following treatment. The acoziborole CPSF3(SNV) SHERLOCK assay discriminated between wild-type CPSF3 RNA and CPSF3 with a single A-C mutation that confers resistance to acoziborole in vitro.
{"title":"A next generation CRISPR diagnostic tool to survey drug resistance in Human African Trypanosomiasis.","authors":"Elena Perez Anton, Annick Dujeancourt-Henry, Brice Rotureau, Lucy Glover","doi":"10.1101/2024.09.15.24313552","DOIUrl":"https://doi.org/10.1101/2024.09.15.24313552","url":null,"abstract":"The WHO aims to eliminate the gambiense form of human African trypanosomiasis (HAT) by 2030. With the decrease of new reported cases, maintaining an efficient epidemiological surveillance is essential, including the emergence of drug-resistant strains. We have developed new highly specific diagnostic tools using Specific High-Sensitivity Reporter Enzymatic UnLOCKing (SHERLOCK) technology for monitoring the presence of drug-resistant genotypes that (1) are already circulating, such as the AQP2/3(814) chimera providing resistance to pentamidine and melarsoprol, or (2) could emerge, such as TbCPSF3 (N232H), associated to acoziborole resistance in lab conditions. The melarsoprol - pentamidine AQP2/3(814) SHERLOCK assay detected RNA from both cultured parasites and field isolated strains from gHAT patients in relapse following treatment. The acoziborole CPSF3(SNV) SHERLOCK assay discriminated between wild-type CPSF3 RNA and CPSF3 with a single A-C mutation that confers resistance to acoziborole in vitro.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265948","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 : 2024-09-16DOI: 10.1101/2024.09.16.24313752
Naomi A Rankin, Samee Saiyed, Hongru Du, Lauren Marie Gardner
The COVID-19 pandemic highlighted shortcomings in forecasting models, such as unreliable inputs/outputs and poor performance at critical points. As COVID-19 remains a threat, it is imperative to improve current forecasting approaches by incorporating reliable data and alternative forecasting targets to better inform decision-makers. Wastewater-based epidemiology (WBE) has emerged as a viable method to track COVID-19 transmission, offering a more reliable metric than reported cases for forecasting critical outcomes like hospitalizations. Recognizing the natural alignment of wastewater systems with city structures, ideal for leveraging WBE data, this study introduces a multi-city, wastewater-based forecasting model to categorically predict COVID-19 hospitalizations.
{"title":"A Multi-City COVID-19 Categorical Forecasting Model Utilizing Wastewater-Based Epidemiology","authors":"Naomi A Rankin, Samee Saiyed, Hongru Du, Lauren Marie Gardner","doi":"10.1101/2024.09.16.24313752","DOIUrl":"https://doi.org/10.1101/2024.09.16.24313752","url":null,"abstract":"The COVID-19 pandemic highlighted shortcomings in forecasting models, such as unreliable inputs/outputs and poor performance at critical points. As COVID-19 remains a threat, it is imperative to improve current forecasting approaches by incorporating reliable data and alternative forecasting targets to better inform decision-makers. Wastewater-based epidemiology (WBE) has emerged as a viable method to track COVID-19 transmission, offering a more reliable metric than reported cases for forecasting critical outcomes like hospitalizations. Recognizing the natural alignment of wastewater systems with city structures, ideal for leveraging WBE data, this study introduces a multi-city, wastewater-based forecasting model to categorically predict COVID-19 hospitalizations.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265695","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}
The Nugent score is a commonly used tool for diagnosing bacterial vaginosis; however, its accuracy depends on the skills of laboratory technicians. We aimed to evaluate the performance of deep learning models in predicting the Nugent score, with the goal of improving diagnostic consistency and accuracy. A total of 1,510 vaginal images collected from a hospital in Japan between 2021 and 2023 were assessed. Each image was annotated by laboratory technicians into one of four categories based on the Nugent—scorenormal vaginal flora, absence of vaginal flora, altered vaginal flora, or bacterial vaginosis. Deep learning models were developed to predict these categories, and their performance was evaluated by comparing the predicted scores with technician annotations. A high magnification model was further optimized and evaluated using an independent test set of 106 images to assess its performance relative to that of the technicians. The deep learning models demonstrated an accuracy of 84% at low magnification and 89% at high magnification in predicting the Nugent score categories. After optimization, the high magnification model achieved 94% accuracy, surpassing the average 92% accuracy of the technicians. The agreement between deep learning model predictions and technician annotations was 92% for normal vaginal flora, 100% for absence of vaginal flora, 91% for altered vaginal flora, and 100% for bacterial vaginosis. The deep learning models demonstrated accuracy comparable to that of laboratory technicians, which indicates their potential utility in improving the diagnostic accuracy of bacterial vaginosis.
{"title":"Deep Learning Models for Predicting the Nugent Score to Diagnose Bacterial Vaginosis","authors":"Naoki Watanabe, Tomohisa Watari, Kenji Akamatsu, Isao Miyatsuka, Yoshihito Otsuka","doi":"10.1101/2024.09.16.24313614","DOIUrl":"https://doi.org/10.1101/2024.09.16.24313614","url":null,"abstract":"The Nugent score is a commonly used tool for diagnosing bacterial vaginosis; however, its accuracy depends on the skills of laboratory technicians. We aimed to evaluate the performance of deep learning models in predicting the Nugent score, with the goal of improving diagnostic consistency and accuracy. A total of 1,510 vaginal images collected from a hospital in Japan between 2021 and 2023 were assessed. Each image was annotated by laboratory technicians into one of four categories based on the Nugent—scorenormal vaginal flora, absence of vaginal flora, altered vaginal flora, or bacterial vaginosis. Deep learning models were developed to predict these categories, and their performance was evaluated by comparing the predicted scores with technician annotations. A high magnification model was further optimized and evaluated using an independent test set of 106 images to assess its performance relative to that of the technicians. The deep learning models demonstrated an accuracy of 84% at low magnification and 89% at high magnification in predicting the Nugent score categories. After optimization, the high magnification model achieved 94% accuracy, surpassing the average 92% accuracy of the technicians. The agreement between deep learning model predictions and technician annotations was 92% for normal vaginal flora, 100% for absence of vaginal flora, 91% for altered vaginal flora, and 100% for bacterial vaginosis. The deep learning models demonstrated accuracy comparable to that of laboratory technicians, which indicates their potential utility in improving the diagnostic accuracy of bacterial vaginosis.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265693","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 : 2024-09-16DOI: 10.1101/2024.09.16.24312510
Juan Carlos Sanchez, Ingrid H Robertson, Victoria A.M. Shinakawa, Xiaojing Su, Wan-chen Tu, Timothy R. Robinson, Megan M. Chang, Andrea Blom, Elena Alfaro, Daniel B. Hatchett, Ayokunle O. Olanrewaju, Ellen R. Wald, Gregory P. DeMuri, Erwin Erwin Berthier, Sanitta Thongpang, Ashleigh B Theberge
The CandyCollect device is a lollipop-inspired open fluidic oral sampling device designed to provide a comfortable user sampling experience. We demonstrate that the CandyCollect device can be coupled with a rapid antigen detection test (RADT) kit designed for Group A Streptococcus (GAS). Through in vitro experiments with pooled saliva spiked with Streptococcus pyogenes we tested various reagents and elution volumes to optimize the RADT readout from CandyCollect device samples. The resulting optimized protocol uses the kit-provided reagents and lateral flow assay (LFA) while replacing the kit′s pharyngeal swab with the CandyCollect device, reducing the elution solution volume, and substituting the tube used for elution to accommodate the CandyCollect device. Positive test results were detected by eye with bacterial concentrations as low as the manufacturer′s ″minimal detection limit″ - 1.5x105 CFU/mL. LFA strips were also scanned and quantified with image analysis software to determine the signal-to-baseline ratio (SBR) and categorize positive test results without human bias. We tested our optimized protocol for integrating CandyCollect and RADT using CandyCollect clinical samples from pediatric patients (n=6) who were previously diagnosed with GAS pharyngitis via pharyngeal swabs tested with RADT as part of their clinical care. The LFA results of these CandyCollect devices and interspersed negative controls were determined by independent observers, with positive results obtained in four of the six participants on at least one LFA replicate. Taken together, our results show that CandyCollect devices from children with GAS pharyngitis can be tested using LFA rapid tests.
{"title":"Integration of Group A Streptococcus Rapid Tests with the Open Fluidic CandyCollect Device","authors":"Juan Carlos Sanchez, Ingrid H Robertson, Victoria A.M. Shinakawa, Xiaojing Su, Wan-chen Tu, Timothy R. Robinson, Megan M. Chang, Andrea Blom, Elena Alfaro, Daniel B. Hatchett, Ayokunle O. Olanrewaju, Ellen R. Wald, Gregory P. DeMuri, Erwin Erwin Berthier, Sanitta Thongpang, Ashleigh B Theberge","doi":"10.1101/2024.09.16.24312510","DOIUrl":"https://doi.org/10.1101/2024.09.16.24312510","url":null,"abstract":"The CandyCollect device is a lollipop-inspired open fluidic oral sampling device designed to provide a comfortable user sampling experience. We demonstrate that the CandyCollect device can be coupled with a rapid antigen detection test (RADT) kit designed for Group A Streptococcus (GAS). Through <em>in vitro</em> experiments with pooled saliva spiked with <em>Streptococcus pyogenes</em> we tested various reagents and elution volumes to optimize the RADT readout from CandyCollect device samples. The resulting optimized protocol uses the kit-provided reagents and lateral flow assay (LFA) while replacing the kit′s pharyngeal swab with the CandyCollect device, reducing the elution solution volume, and substituting the tube used for elution to accommodate the CandyCollect device. Positive test results were detected by eye with bacterial concentrations as low as the manufacturer′s ″minimal detection limit″ - 1.5x10<sup>5</sup> CFU/mL. LFA strips were also scanned and quantified with image analysis software to determine the signal-to-baseline ratio (SBR) and categorize positive test results without human bias. We tested our optimized protocol for integrating CandyCollect and RADT using CandyCollect clinical samples from pediatric patients (n=6) who were previously diagnosed with GAS pharyngitis via pharyngeal swabs tested with RADT as part of their clinical care. The LFA results of these CandyCollect devices and interspersed negative controls were determined by independent observers, with positive results obtained in four of the six participants on at least one LFA replicate. Taken together, our results show that CandyCollect devices from children with GAS pharyngitis can be tested using LFA rapid tests.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265692","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 : 2024-09-16DOI: 10.1101/2024.09.16.24313749
Kelsey Shaw, Jennifer Peterson, Neda Jalali, Saikanth Ratnavale, Manar Alkuzweny, Carly Barbera, Alan Costello, Liam Emerick, Guido Espana, Alexander Meyer, Stacy Mowry, Marya Poterek, Carol de Souza Moreira, Eric Morgan, Sean M Moore, Alex Perkins
Historically, most mathematical models of infectious disease dynamics have focused on a single pathogen, despite the ubiquity of co-circulating pathogens in the real world. We conducted a systematic review of 311 published papers that included a mechanistic, population-level model of co-circulating human pathogens. We identified the types of pathogens represented in this literature, techniques used, and motivations for conducting these studies. We also created a complexity index to quantify the degree to which co-circulating pathogen models diverged from single-pathogen models. We found that the emergence of new pathogens, such as HIV and SARS-CoV-2, precipitated modeling activity of the emerging pathogen with established pathogens. Pathogen characteristics also tended to drive modeling activity; for example, HIV suppresses the immune response, eliciting interesting dynamics when it is modeled with other pathogens. The motivations driving these studies were varied but could be divided into two major categories: exploration of dynamics and evaluation of interventions. Finally, we found that model complexity quickly increases as additional pathogens are added. Future potential avenues of research we identified include investigating the effects of misdiagnosis of clinically similar co-circulating pathogens and characterizing the impacts of one pathogen on public health resources available to curtail the spread of other pathogens.
{"title":"Co-circulating pathogens of humans: A systematic review of mechanistic transmission models","authors":"Kelsey Shaw, Jennifer Peterson, Neda Jalali, Saikanth Ratnavale, Manar Alkuzweny, Carly Barbera, Alan Costello, Liam Emerick, Guido Espana, Alexander Meyer, Stacy Mowry, Marya Poterek, Carol de Souza Moreira, Eric Morgan, Sean M Moore, Alex Perkins","doi":"10.1101/2024.09.16.24313749","DOIUrl":"https://doi.org/10.1101/2024.09.16.24313749","url":null,"abstract":"Historically, most mathematical models of infectious disease dynamics have focused on a single pathogen, despite the ubiquity of co-circulating pathogens in the real world. We conducted a systematic review of 311 published papers that included a mechanistic, population-level model of co-circulating human pathogens. We identified the types of pathogens represented in this literature, techniques used, and motivations for conducting these studies. We also created a complexity index to quantify the degree to which co-circulating pathogen models diverged from single-pathogen models. We found that the emergence of new pathogens, such as HIV and SARS-CoV-2, precipitated modeling activity of the emerging pathogen with established pathogens. Pathogen characteristics also tended to drive modeling activity; for example, HIV suppresses the immune response, eliciting interesting dynamics when it is modeled with other pathogens. The motivations driving these studies were varied but could be divided into two major categories: exploration of dynamics and evaluation of interventions. Finally, we found that model complexity quickly increases as additional pathogens are added. Future potential avenues of research we identified include investigating the effects of misdiagnosis of clinically similar co-circulating pathogens and characterizing the impacts of one pathogen on public health resources available to curtail the spread of other pathogens.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265694","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 : 2024-09-16DOI: 10.1101/2024.09.14.24313675
Shramana Deb, Ritwick Mondal, Purbita Sen, Dipanjan Chowdhury, Shramana Sarkar, Granthik Banerjee, Vramanti Sarkar, Anjan Chowdhury, Julian Benito-Leon
Background: The Monkeypox virus, a zoonotic pathogen of the Orthopoxvirus genus, has shown a marked global spread, resulting in cases of neuroinflammatory disorders. This systematic review aims to summarize the central nervous system manifestations linked to monkeypox virus infection. Methods: We conducted a systematic review according to PRISMA guidelines. Databases such as PubMed, EMBASE, Cochrane Library, and Web of Science were searched up to September 2024. Inclusion criteria focused on monkeypox virus-positive patients with confirmed central nervous system inflammatory disorders, including encephalitis, meningitis, myelitis, and related neuroimmune diseases. Results: From 770 screened articles, 38 studies were included. Of the 20 reported monkeypox virus-infected cases with central nervous system involvement, the most common manifestations were encephalitis (40%), encephalomyelitis (30%), and meningoencephalitis (10%). Additional rarer presentations included Guillain-Barre syndrome (5%) and transverse myelitis (5%). The mean age of affected individuals was 27.9 years, and 75% were male. Fever, fatigue, and myalgia were the predominant systemic symptoms, with neurological complications often appearing within 4.6 days post-infection. Diagnoses were confirmed by quantitative reverse transcription polymerase chain reaction, magnetic resonance imaging, and cerebrospinal fluid analysis. Treatment strategies varied, with antivirals (e.g., tecovirimat) and immunomodulatory therapies (e.g., methylprednisolone, immunoglobulins, and rituximab) utilized. Conclusions: Monkeypox virus infection is associated with severe neuroinflammatory disorders, with varying outcomes from complete recovery to mortality. Increased awareness, comprehensive diagnostic approaches, and targeted therapeutic interventions are critical in managing these cases. Further research is required to elucidate the mechanisms of neuroinflammation in the monkeypox virus and establish standardized treatment protocols.
{"title":"Neuroinflammatory Disorders of the Central Nervous System Associated with Monkeypox Virus Infection: A Systematic Review and Call to Action","authors":"Shramana Deb, Ritwick Mondal, Purbita Sen, Dipanjan Chowdhury, Shramana Sarkar, Granthik Banerjee, Vramanti Sarkar, Anjan Chowdhury, Julian Benito-Leon","doi":"10.1101/2024.09.14.24313675","DOIUrl":"https://doi.org/10.1101/2024.09.14.24313675","url":null,"abstract":"Background: The Monkeypox virus, a zoonotic pathogen of the Orthopoxvirus genus, has shown a marked global spread, resulting in cases of neuroinflammatory disorders. This systematic review aims to summarize the central nervous system manifestations linked to monkeypox virus infection.\u0000Methods: We conducted a systematic review according to PRISMA guidelines. Databases such as PubMed, EMBASE, Cochrane Library, and Web of Science were searched up to September 2024. Inclusion criteria focused on monkeypox virus-positive patients with confirmed central nervous system inflammatory disorders, including encephalitis, meningitis, myelitis, and related neuroimmune diseases.\u0000Results: From 770 screened articles, 38 studies were included. Of the 20 reported monkeypox virus-infected cases with central nervous system involvement, the most common manifestations were encephalitis (40%), encephalomyelitis (30%), and meningoencephalitis (10%). Additional rarer presentations included Guillain-Barre syndrome (5%) and transverse myelitis (5%). The mean age of affected individuals was 27.9 years, and 75% were male. Fever, fatigue, and myalgia were the predominant systemic symptoms, with neurological complications often appearing within 4.6 days post-infection. Diagnoses were confirmed by quantitative reverse transcription polymerase chain reaction, magnetic resonance imaging, and cerebrospinal fluid analysis. Treatment strategies varied, with antivirals (e.g., tecovirimat) and immunomodulatory therapies (e.g., methylprednisolone, immunoglobulins, and rituximab) utilized.\u0000Conclusions: Monkeypox virus infection is associated with severe neuroinflammatory disorders, with varying outcomes from complete recovery to mortality. Increased awareness, comprehensive diagnostic approaches, and targeted therapeutic interventions are critical in managing these cases. Further research is required to elucidate the mechanisms of neuroinflammation in the monkeypox virus and establish standardized treatment protocols.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265698","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 : 2024-09-16DOI: 10.1101/2024.09.12.24313188
Daniel Mukadi-Bamuleka, Eddy Kinganda Lusamaki, Noella Mulopo-Mukanya, Adrienne Amuri-Aziza, Aine O'Toole, Brigitte Modadra-Madakpa, Guy Mutombo-Ndongala, Emmanuel Hasivirwe Vakaniaki, Sydney Merritt, Cris Kacita, Gaston Lubambo Maboko, Jean Claude Makangara, Michel Ngimba, Emmanuel Lokilo, Elisabeth Pukuta-Simbu, Gradi Luakanda-Ndelemo, Tavia Bodisa-Matamu, Zephanie Paluku-Kalimuli, Prince Akil-Bandali, Sifa Kavira, Daan Jansen, Adele Kavira-Kamaliro, Emile Muhindo-Milonde, Jeriel Mufungizi, Yves Birindwa Hamisi, Hugo Kavunga-Membo, Olivier Tshiani, Sabin S Nundu, Laurens Liesenborghs, Nicole A Hoff, Jean B Nachega, Robert Shongo, Ahidjo Ayouba, Genay Pilarowski, Alain Kakule Mangolopa, Amos K. Ebondo, Nicola Low, Souradet Y. Shaw, Sam AJ Wilkinson, Sofonias Kifle Tessema, Lorenzo Subissi, Eric Delaporte, Koen Vercauteren, Tony Wawina-Bokalanga, Anne W. Rimoin, Martine Peeters, Nicholas James Loman, Andrew Rambaut, Jean-Jacques Tamfum Muyembe, Lisa E Hensley, Jason Kindrachuk, Mbala Placide, Steve Ahuka-Mundeke
The ongoing national mpox outbreak in the Democratic Republic of the Congo has resulted in more >30,000 suspected cases in the country from January 2023 to August 2024. While these historic case totals have been driven by primarily by zoonosis, the emergence of Clade Ib monkeypox virus (MPXV), which is connected to more sustained human-to-human transmission, has been associated with increasing public health impacts in eastern DRC. First identified in South Kivu province, Clade Ib MPXV has been identified in multiple non-endemic East African countries for the first time. In DRC, there have been concerns over broader Clade Ib expansion in the country that could further complicate containment and mitigation responses. Here, we report the first introductions of Clade Ib into North Kivu province, including within internal displacement camps, with suspected close contact transmission that includes non-intimate contacts and children. These findings demonstrate that mpox case investigations and community messaging campaigns should include considerations for non-sexual contact-mediated transmission of Clade Ib that includes children <15 years.
{"title":"First imported Cases of MPXV Clade Ib in Goma, Democratic Republic of the Congo: Implications for Global Surveillance and Transmission Dynamics","authors":"Daniel Mukadi-Bamuleka, Eddy Kinganda Lusamaki, Noella Mulopo-Mukanya, Adrienne Amuri-Aziza, Aine O'Toole, Brigitte Modadra-Madakpa, Guy Mutombo-Ndongala, Emmanuel Hasivirwe Vakaniaki, Sydney Merritt, Cris Kacita, Gaston Lubambo Maboko, Jean Claude Makangara, Michel Ngimba, Emmanuel Lokilo, Elisabeth Pukuta-Simbu, Gradi Luakanda-Ndelemo, Tavia Bodisa-Matamu, Zephanie Paluku-Kalimuli, Prince Akil-Bandali, Sifa Kavira, Daan Jansen, Adele Kavira-Kamaliro, Emile Muhindo-Milonde, Jeriel Mufungizi, Yves Birindwa Hamisi, Hugo Kavunga-Membo, Olivier Tshiani, Sabin S Nundu, Laurens Liesenborghs, Nicole A Hoff, Jean B Nachega, Robert Shongo, Ahidjo Ayouba, Genay Pilarowski, Alain Kakule Mangolopa, Amos K. Ebondo, Nicola Low, Souradet Y. Shaw, Sam AJ Wilkinson, Sofonias Kifle Tessema, Lorenzo Subissi, Eric Delaporte, Koen Vercauteren, Tony Wawina-Bokalanga, Anne W. Rimoin, Martine Peeters, Nicholas James Loman, Andrew Rambaut, Jean-Jacques Tamfum Muyembe, Lisa E Hensley, Jason Kindrachuk, Mbala Placide, Steve Ahuka-Mundeke","doi":"10.1101/2024.09.12.24313188","DOIUrl":"https://doi.org/10.1101/2024.09.12.24313188","url":null,"abstract":"The ongoing national mpox outbreak in the Democratic Republic of the Congo has resulted in more >30,000 suspected cases in the country from January 2023 to August 2024. While these historic case totals have been driven by primarily by zoonosis, the emergence of Clade Ib monkeypox virus (MPXV), which is connected to more sustained human-to-human transmission, has been associated with increasing public health impacts in eastern DRC. First identified in South Kivu province, Clade Ib MPXV has been identified in multiple non-endemic East African countries for the first time. In DRC, there have been concerns over broader Clade Ib expansion in the country that could further complicate containment and mitigation responses. Here, we report the first introductions of Clade Ib into North Kivu province, including within internal displacement camps, with suspected close contact transmission that includes non-intimate contacts and children. These findings demonstrate that mpox case investigations and community messaging campaigns should include considerations for non-sexual contact-mediated transmission of Clade Ib that includes children <15 years.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265696","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 : 2024-09-15DOI: 10.1101/2024.09.14.24313671
Siyue Jia, Yuanbao Liu, Qian He, Hongxing Pan, Zhenglun Liang, Juan Zhou, Yingzi Pan, Sheng Liu, Jingjing Wu, Kun Yang, Xuanxuan Zhang, Yang Zhao, Simin Li, Lei Zhang, Li Chen, Aihua Yao, Mengyi Lu, Qunying Mao, Fengcai Zhu, Jingxin Li
Background The primary objective of this research was to assess if a booster dose with COVID-19 vaccines containing ancestral strain could still provide significant protection against symptomatic SARS-CoV-2 infection in a predominantly hybrid-immune population during the period of omicron variant dominance. Methods We did a multicenter, partially randomized, platform trial to evaluate the effectiveness of a booster dose of an aerosolized or intramuscular adenovirus type 5 vectored COVID-19 vaccine (Ad5-nCoV) in adults, after the national-wide omicron circulating at the end of year 2022 in China. Participants who were willing to receive a COVID-19 booster dose were randomly assigned to receive one of the booster doses. While, those participants who refused to take a booster dose but consented to participate COVID-19 surveillance were included in a control group. Both participants receiving a booster dose or not were monitored for symptomatic COVID-19 during a six-month surveillance period. Results Between May 23, 2023, and August 28, 2023, 4089 eligible participants were equally randomized to receive a booster dose of aerosolized Ad5-nCoV through oral inhalation at 0.1mL (IH Ad5-nCoV, n=2039) or intramuscular injection of Ad5-nCoV at 0.5 mL (IM Ad5-nCoV, n=2050). While, 2008 participants were enrolled in the blank-control group. A total of 79 COVID-19 cases were confirmed, with 22 (0.006%) in the IH Ad5-nCoV group, 23 (0.007%) in the IM Ad5-nCoV group, and 34 (0.01%) in the control group. Adjusted effectiveness of IH Ad5-nCoV and IM Ad5-nCoV from 14 days after the vaccination were 51.6% (95% CI 9.0 to 74.3) and 38.1% (95% CI -9.6 to 65.1), respectively. Interpretation Significant protection against symptomatic COVID-19 caused by the Omicron variant, during the ongoing pandemic of evolving COVID-19 variants, was found to be provided by boosting with the ancestral strain-containing vaccine IH Ad5-nCoV, but not by boosting with IM Ad5-nCoV.
{"title":"Effectiveness of a booster dose of aerosolized or intramuscular adenovirus type 5 vectored COVID-19 vaccine in adults with hybrid immunity against COVID-19: a multicenter, partially randomized, platform trial in China","authors":"Siyue Jia, Yuanbao Liu, Qian He, Hongxing Pan, Zhenglun Liang, Juan Zhou, Yingzi Pan, Sheng Liu, Jingjing Wu, Kun Yang, Xuanxuan Zhang, Yang Zhao, Simin Li, Lei Zhang, Li Chen, Aihua Yao, Mengyi Lu, Qunying Mao, Fengcai Zhu, Jingxin Li","doi":"10.1101/2024.09.14.24313671","DOIUrl":"https://doi.org/10.1101/2024.09.14.24313671","url":null,"abstract":"Background The primary objective of this research was to assess if a booster dose with COVID-19 vaccines containing ancestral strain could still provide significant protection against symptomatic SARS-CoV-2 infection in a predominantly hybrid-immune population during the period of omicron variant dominance. Methods We did a multicenter, partially randomized, platform trial to evaluate the effectiveness of a booster dose of an aerosolized or intramuscular adenovirus type 5 vectored COVID-19 vaccine (Ad5-nCoV) in adults, after the national-wide omicron circulating at the end of year 2022 in China. Participants who were willing to receive a COVID-19 booster dose were randomly assigned to receive one of the booster doses. While, those participants who refused to take a booster dose but consented to participate COVID-19 surveillance were included in a control group. Both participants receiving a booster dose or not were monitored for symptomatic COVID-19 during a six-month surveillance period. Results Between May 23, 2023, and August 28, 2023, 4089 eligible participants were equally randomized to receive a booster dose of aerosolized Ad5-nCoV through oral inhalation at 0.1mL (IH Ad5-nCoV, n=2039) or intramuscular injection of Ad5-nCoV at 0.5 mL (IM Ad5-nCoV, n=2050). While, 2008 participants were enrolled in the blank-control group. A total of 79 COVID-19 cases were confirmed, with 22 (0.006%) in the IH Ad5-nCoV group, 23 (0.007%) in the IM Ad5-nCoV group, and 34 (0.01%) in the control group. Adjusted effectiveness of IH Ad5-nCoV and IM Ad5-nCoV from 14 days after the vaccination were 51.6% (95% CI 9.0 to 74.3) and 38.1% (95% CI -9.6 to 65.1), respectively. Interpretation Significant protection against symptomatic COVID-19 caused by the Omicron variant, during the ongoing pandemic of evolving COVID-19 variants, was found to be provided by boosting with the ancestral strain-containing vaccine IH Ad5-nCoV, but not by boosting with IM Ad5-nCoV.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265697","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}
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