Pub Date : 2024-07-26DOI: 10.1101/2024.07.24.24310905
Ji Youn Lim, Alyssa Fiore, Bruce Le, Corinne Minzer, Halle White, Krystle Burinski, Humaira Janwari, David Wright, Sasha Perebikovsky, Ralph Davis, David Okrongly, Aravind Srinivasan
Neutralizing antibody titer elicited through infection or vaccination is accepted as a reliable surrogate for protection from SARS-CoV-2 infection, hospitalization, and mortality. The gold standard for measuring neutralizing antibody levels relies on culturing live virus in the presence of a target cell and quantitating the level where 50% of the target cells are infected. These assays have numerous technical challenges, not the least is the requirement for a BSL-3 laboratory to perform the live virus testing. We developed the Q-NAb IgG Test for the quantitative determination of neutralizing antibodies against SARS-CoV-2 variants, traceable to WHO International Standards. The test utilizes a novel Fusion Protein that mimics the Spike receptor binding domain docked to the human ACE2 protein and effectively blocks non-neutralizing antibodies in the sample. After pre-blocking sequesters the non-neutralizing antibodies from the samples, direct binding of the residual neutralizing antibodies to variant RBDs coated in the wells of the microtiter plate is measured with a fluorescent secondary antibody. Results of the Q-NAb IgG Test agree with a live virus Microneutralization Assay for both the Ancestral strain (WA1-2020) and the Omicron BA.5 (COR-22-063113/2022) variant (Spearmans correlation, ρ = 0.87 and 0.92, respectively). The analytical performance (LoB, LoD, LoQ, linearity, precision, and interference) of the Q-NAb IgG Test was established along with sensitivity and specificity using a panel of monoclonal neutralizing and non-neutralizing anti-SARS-CoV-2 antibodies. Clinical sensitivity and specificity using pre-pandemic, convalescent, and vaccinated serum and plasma samples is also reported. The advantages of the Q-NAb IgG Test are its strong correlation to live virus neutralization tests, traceability to WHO International Standards, convenient microtiter plate format, low sample volume requirements, and suitability for a BSL-2 laboratory.
{"title":"Development and Validation of Novel Cell-free Direct Neutralization Assay for SARS-CoV-2","authors":"Ji Youn Lim, Alyssa Fiore, Bruce Le, Corinne Minzer, Halle White, Krystle Burinski, Humaira Janwari, David Wright, Sasha Perebikovsky, Ralph Davis, David Okrongly, Aravind Srinivasan","doi":"10.1101/2024.07.24.24310905","DOIUrl":"https://doi.org/10.1101/2024.07.24.24310905","url":null,"abstract":"Neutralizing antibody titer elicited through infection or vaccination is accepted as a reliable surrogate for protection from SARS-CoV-2 infection, hospitalization, and mortality. The gold standard for measuring neutralizing antibody levels relies on culturing live virus in the presence of a target cell and quantitating the level where 50% of the target cells are infected. These assays have numerous technical challenges, not the least is the requirement for a BSL-3 laboratory to perform the live virus testing. We developed the Q-NAb IgG Test for the quantitative determination of neutralizing antibodies against SARS-CoV-2 variants, traceable to WHO International Standards. The test utilizes a novel Fusion Protein that mimics the Spike receptor binding domain docked to the human ACE2 protein and effectively blocks non-neutralizing antibodies in the sample. After pre-blocking sequesters the non-neutralizing antibodies from the samples, direct binding of the residual neutralizing antibodies to variant RBDs coated in the wells of the microtiter plate is measured with a fluorescent secondary antibody. Results of the Q-NAb IgG Test agree with a live virus Microneutralization Assay for both the Ancestral strain (WA1-2020) and the Omicron BA.5 (COR-22-063113/2022) variant (Spearmans correlation, ρ = 0.87 and 0.92, respectively). The analytical performance (LoB, LoD, LoQ, linearity, precision, and interference) of the Q-NAb IgG Test was established along with sensitivity and specificity using a panel of monoclonal neutralizing and non-neutralizing anti-SARS-CoV-2 antibodies. Clinical sensitivity and specificity using pre-pandemic, convalescent, and vaccinated serum and plasma samples is also reported. The advantages of the Q-NAb IgG Test are its strong correlation to live virus neutralization tests, traceability to WHO International Standards, convenient microtiter plate format, low sample volume requirements, and suitability for a BSL-2 laboratory.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141786230","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 : 2024-07-26DOI: 10.1101/2024.07.25.24310996
Dilip Abraham, Lalithambigai Kathiresan, Kristen Aiemjoy, Richelle C Charles, Dilesh Kumar, Rajan Srinivasan, Catherine Troman, Elizabeth Gray, Christopher B Uzzell, Jacob John, Balaji Veeraraghavan, Nicholas Grassly, Venkata Raghava Mohan
Background Blood culture based surveillance for typhoid fever has limited sensitivity, encountering operational challenges in resource-limited settings. Environmental surveillance targeting Salmonella Typhi (S. Typhi) shed in wastewater (WW), coupled with cross-sectional serosurveys of S. Typhi specific antibodies estimating exposure to infection, emerges as a promising alternative. Methods We assessed the feasibility and effectiveness of wastewater (WW) and sero-surveillance for S. Typhi in Vellore, India, from May 2022 to April 2023. Monthly samples were collected from 40 sites in open drainage channels and processed using standardized protocols. DNA was extracted and analyzed via quantitative PCR for S. Typhi genes (ttr, tviB, staG) and the fecal biomarker HF183. Clinical cases of enteric fever were recorded from four major hospitals, and a crosssectional serosurvey measured hemolysin E (HlyE) IgG levels in children under 15 years to estimate seroincidence. Results 7.5% (39/520) of grab and 15.3% (79/517) Moore swabs were positive for all 3 S . Typhi genes. Moore swab positivity was significantly associated with HF183 (adjusted odds ratio (aOR): 3.08, 95% CI: 1.59, 5.93) and upstream catchment population (aOR: 4.67, 1.97, 11.04), and there was increased detection during monsoon season, membrane filtration (aOR: 2.56, 1.02, 6.41), and Moore swab samples (aOR: 2.03, 1.01, 3.97). Only 11 blood culture-confirmed typhoid cases were documented over the study period. Estimated seroincidence was 10.4/100 person-years (py) (95% CI: 9.61, 11.5/100 py). The number of S. Typhi positive samples at a site was associated with the estimated sero-incidence in the site catchment population (incidence rate ratios: 1.14 (1.07, 1.23) and 1.10 (1.02, 1.20) for grab and Moore swabs respectively. Conclusions These findings underscore the utility and effectiveness of alternate surveillance approaches to estimating the incidence of S. Typhi infection in resource-limited settings, offering valuable insights for public health interventions and disease monitoring strategies where conventional methods are challenging to implement.
{"title":"Wastewater surveillance for Salmonella Typhi and its association with seroincidence of enteric fever in Vellore, India","authors":"Dilip Abraham, Lalithambigai Kathiresan, Kristen Aiemjoy, Richelle C Charles, Dilesh Kumar, Rajan Srinivasan, Catherine Troman, Elizabeth Gray, Christopher B Uzzell, Jacob John, Balaji Veeraraghavan, Nicholas Grassly, Venkata Raghava Mohan","doi":"10.1101/2024.07.25.24310996","DOIUrl":"https://doi.org/10.1101/2024.07.25.24310996","url":null,"abstract":"Background Blood culture based surveillance for typhoid fever has limited sensitivity, encountering operational challenges in resource-limited settings. Environmental surveillance targeting Salmonella Typhi (S. Typhi) shed in wastewater (WW), coupled with cross-sectional serosurveys of S. Typhi specific antibodies estimating exposure to infection, emerges as a promising alternative. Methods\u0000We assessed the feasibility and effectiveness of wastewater (WW) and sero-surveillance for S. Typhi in Vellore, India, from May 2022 to April 2023. Monthly samples were collected from 40 sites in open drainage channels and processed using standardized protocols. DNA was extracted and analyzed via quantitative PCR for S. Typhi genes (ttr, tviB, staG) and the fecal biomarker HF183. Clinical cases of enteric fever were recorded from four major hospitals, and a crosssectional serosurvey measured hemolysin E (HlyE) IgG levels in children under 15 years to estimate seroincidence.\u0000Results\u00007.5% (39/520) of grab and 15.3% (79/517) Moore swabs were positive for all 3 S . Typhi genes. Moore swab positivity was significantly associated with HF183 (adjusted odds ratio (aOR): 3.08, 95% CI: 1.59, 5.93) and upstream catchment population (aOR: 4.67, 1.97, 11.04), and there was increased detection during monsoon season, membrane filtration (aOR: 2.56, 1.02, 6.41), and Moore swab samples (aOR: 2.03, 1.01, 3.97). Only 11 blood culture-confirmed typhoid cases were documented over the study period. Estimated seroincidence was 10.4/100 person-years (py) (95% CI: 9.61, 11.5/100 py). The number of S. Typhi positive samples at a site was associated with the estimated sero-incidence in the site catchment population (incidence rate ratios: 1.14 (1.07, 1.23) and 1.10 (1.02, 1.20) for grab and Moore swabs respectively.\u0000Conclusions\u0000These findings underscore the utility and effectiveness of alternate surveillance approaches to estimating the incidence of S. Typhi infection in resource-limited settings, offering valuable insights for public health interventions and disease monitoring strategies where conventional methods are challenging to implement.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141783385","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 : 2024-07-26DOI: 10.1101/2024.07.25.24311029
Jamie L Dombach, Nancy Smith, Teresa Kottiri, Alicia M Schiller, Edwin Kamau
Uncomplicated bacteremic urinary tract infections (bUTIs) are common, often caused by Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecalis, with most encounters treated empirically. As rates of antimicrobial resistance increase, available antibiotic treatment options are dwindling. Novel antibiotics approved for treating bUTIs are limited, leading to a resurgence of interest in older antibiotics, including fosfomycin. In this study, clinical urine samples from patients diagnosed with bUTIs from a military hospital on the Eastern Seaboard of the United States were tested for susceptibility to fosfomycin and comparator antibiotics, including levofloxacin, nitrofurantoin, and trimethoprim-sulfamethoxazole (TMS). A total of 1353 nonduplicate bacterial isolates were tested. The majority were Gram-negative, including 605 non-ESBL and 285 ESBL E. coli and 84 non-ESBL and 52 ESBL K. pneumoniae. Fosfomycin susceptibility rates were similar for non-ESBL and ESBL E. coli (95.9% vs 96.1%) and K. pneumoniae (38.1% vs 36.5%). Fosfomycin demonstrated high activity against other Enterobacterales and Gram-positive organisms including Enterobacter faecalis and Staphylococcus aureus. Interestingly, most fosfomycin non-susceptible isolates were susceptible to other first-line bUTI treatment options, and most isolates that were non-susceptible to other first-line bUTI treatment option were susceptible to fosfomycin. ESBL K. pneumoniae isolates were the least susceptible to current first-line treatment options. Fosfomycin Etest demonstrated high sensitivity compared to agar dilution, making it a viable method in resource limited areas. Overall, we demonstrated fosfomycin has high activity against common etiologies that cause bUTIs. Further studies investigating the use of fosfomycin in treating non-E. coli bUTI pathogens, as single or combination therapy, is warranted.
{"title":"Antimicrobial Susceptibilities of Clinical Bacterial Isolates from Urinary Tract Infections to Fosfomycin and Comparator Antibiotics Determined by Agar Dilution Method and Automated Micro Broth Dilution","authors":"Jamie L Dombach, Nancy Smith, Teresa Kottiri, Alicia M Schiller, Edwin Kamau","doi":"10.1101/2024.07.25.24311029","DOIUrl":"https://doi.org/10.1101/2024.07.25.24311029","url":null,"abstract":"Uncomplicated bacteremic urinary tract infections (bUTIs) are common, often caused by Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecalis, with most encounters treated empirically. As rates of antimicrobial resistance increase, available antibiotic treatment options are dwindling. Novel antibiotics approved for treating bUTIs are limited, leading to a resurgence of interest in older antibiotics, including fosfomycin. In this study, clinical urine samples from patients diagnosed with bUTIs from a military hospital on the Eastern Seaboard of the United States were tested for susceptibility to fosfomycin and comparator antibiotics, including levofloxacin, nitrofurantoin, and trimethoprim-sulfamethoxazole (TMS). A total of 1353 nonduplicate bacterial isolates were tested. The majority were Gram-negative, including 605 non-ESBL and 285 ESBL E. coli and 84 non-ESBL and 52 ESBL K. pneumoniae. Fosfomycin susceptibility rates were similar for non-ESBL and ESBL E. coli (95.9% vs 96.1%) and K. pneumoniae (38.1% vs 36.5%). Fosfomycin demonstrated high activity against other Enterobacterales and Gram-positive organisms including Enterobacter faecalis and Staphylococcus aureus. Interestingly, most fosfomycin non-susceptible isolates were susceptible to other first-line bUTI treatment options, and most isolates that were non-susceptible to other first-line bUTI treatment option were susceptible to fosfomycin. ESBL K. pneumoniae isolates were the least susceptible to current first-line treatment options. Fosfomycin Etest demonstrated high sensitivity compared to agar dilution, making it a viable method in resource limited areas. Overall, we demonstrated fosfomycin has high activity against common etiologies that cause bUTIs. Further studies investigating the use of fosfomycin in treating non-E. coli bUTI pathogens, as single or combination therapy, is warranted.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141783383","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 : 2024-07-26DOI: 10.1101/2024.07.25.24311011
Armand Mayindu Mambote, John Bwalya Muma, Mary Mubiana, Steward Mudenda, Victor Daka, Melai Mubanga, Flavien Nsoni Bumbangi, Chanda Chitalu, Ruth Lindizyani Mfune
Introduction: Brucellosis is a neglected zoonotic disease that affects humans and animals and can lead to severe illness in humans and financial losses for households that rear livestock. The study aimed to investigate the seroprevalence of human Brucella antibodies and associated risk factors among patients seeking medical attention at community hospitals. Methods: A cross-sectional seroepidemiological study was conducted from 21st April 2021 to 21st April 2024 among patients seeking medical attention at community hospitals in selected districts of Western province in Zambia. 225 blood samples were collected from consenting participants. Sera were separated and analysed for anti-Brucella antibodies using the Rose Bengal Test (RBT) and Competitive enzyme-linked immunosorbent assay (c-ELISA) in parallel. A questionnaire was administered to obtain epidemiological data related to exposure to the Brucella pathogen. The data obtained were coded and entered in the Micro-Soft Excel 2013® and analysed using STATA version 15®. Results: 197 sera samples were found acceptable for testing and analysis for this study, out of these, the seroprevalence of Brucella antibodies was 18.3% (n=36, 95% CI=0.13-0.24) and 4.57% (n=9, 95% CI=-0.68-0.28) on RBT and c-ELISA respectively.Among the risk factors considered, the number of animals was statistically significantly associated with Brucella seropositivity (OR 6.49, 95% CI=1.10-38.13, p-value = 0.039). Conclusions: Brucella antibodies are prevalent among patients attending health facilities in the Western province of Zambia. The number of animals were significantly associated with the Brucella seropositivity.
{"title":"Seroprevalence of Human Brucella Antibodies and associated Risk Factors Among Patients Seeking Medical Attention at Community Hospitals in Selected Districts of Western Province in Zambia","authors":"Armand Mayindu Mambote, John Bwalya Muma, Mary Mubiana, Steward Mudenda, Victor Daka, Melai Mubanga, Flavien Nsoni Bumbangi, Chanda Chitalu, Ruth Lindizyani Mfune","doi":"10.1101/2024.07.25.24311011","DOIUrl":"https://doi.org/10.1101/2024.07.25.24311011","url":null,"abstract":"Introduction: Brucellosis is a neglected zoonotic disease that affects humans and animals and can lead to severe illness in humans and financial losses for households that rear livestock. The study aimed to investigate the seroprevalence of human Brucella antibodies and associated risk factors among patients seeking medical attention at community hospitals.\u0000Methods: A cross-sectional seroepidemiological study was conducted from 21st April 2021 to 21st April 2024 among patients seeking medical attention at community hospitals in selected districts of Western province in Zambia. 225 blood samples were collected from consenting participants. Sera were separated and analysed for anti-Brucella antibodies using the Rose Bengal Test (RBT) and Competitive enzyme-linked immunosorbent assay (c-ELISA) in parallel. A questionnaire was administered to obtain epidemiological data related to exposure to the Brucella pathogen. The data obtained were coded and entered in the Micro-Soft Excel 2013® and analysed using STATA version 15®.\u0000Results: 197 sera samples were found acceptable for testing and analysis for this study, out of these, the seroprevalence of Brucella antibodies was 18.3% (n=36, 95% CI=0.13-0.24) and 4.57% (n=9, 95% CI=-0.68-0.28) on RBT and c-ELISA respectively.Among the risk factors considered, the number of animals was statistically significantly associated with Brucella seropositivity (OR 6.49, 95% CI=1.10-38.13, p-value = 0.039). Conclusions: Brucella antibodies are prevalent among patients attending health facilities in the Western province of Zambia. The number of animals were significantly associated with the Brucella seropositivity.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141783386","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 : 2024-07-26DOI: 10.1101/2024.07.25.24310990
Bo Konings, Luisa Villatoro, Robert Burns, Guillermo Barahona, Megan McKnight, Ken Hui, Jan Tack, Pankaj Jay Pasricha
COVID-19 increases the risk of neurological and gastrointestinal sequelae, but it is unclear if it does so more than other infections. Using a multicenter record network, we matched 649,478 COVID-19 patients to negative controls (NCs) and patients infected with influenza, human herpesvirusses, and lyme's disease (LD) to compare new-onset gastrointestinal (GISx), autonomic (ANSx), sensory (SNSx), and motor (MNSx) symptoms 3-12 months after infection. ANSx showed significant increases compared to NCs (odds ratio (OR) 1.34; confidence interval (CI) 1.31-1.36) and most other investigated infections (LD, influenza, infectious mononucleosis, and herpes zoster; OR 1.40, 1.13, 1.11, and 1.05, respectively). SNSx (OR 1.35; CI 1.31-1.39), MNSx (OR 1.32; CI 1.28-1.36) and GISx (OR 1.36; CI 1.33-1.38) were increased but varied more compared with other infections. COVID-19 vaccination reduced the risk of GISx, ANSx, and SNSx. Sequelae frequently ascribed to COVID-19 may manifest with similar or higher frequency after other infections, except ANSx.
{"title":"Long-term neurological and gastrointestinal sequelae of SARS-CoV-2, influenza, and other neurotropic infections with and without vaccination","authors":"Bo Konings, Luisa Villatoro, Robert Burns, Guillermo Barahona, Megan McKnight, Ken Hui, Jan Tack, Pankaj Jay Pasricha","doi":"10.1101/2024.07.25.24310990","DOIUrl":"https://doi.org/10.1101/2024.07.25.24310990","url":null,"abstract":"COVID-19 increases the risk of neurological and gastrointestinal sequelae, but it is unclear if it does so more than other infections. Using a multicenter record network, we matched 649,478 COVID-19 patients to negative controls (NCs) and patients infected with influenza, human herpesvirusses, and lyme's disease (LD) to compare new-onset gastrointestinal (GISx), autonomic (ANSx), sensory (SNSx), and motor (MNSx) symptoms 3-12 months after infection. ANSx showed significant increases compared to NCs (odds ratio (OR) 1.34; confidence interval (CI) 1.31-1.36) and most other investigated infections (LD, influenza, infectious mononucleosis, and herpes zoster; OR 1.40, 1.13, 1.11, and 1.05, respectively). SNSx (OR 1.35; CI 1.31-1.39), MNSx (OR 1.32; CI 1.28-1.36) and GISx (OR 1.36; CI 1.33-1.38) were increased but varied more compared with other infections. COVID-19 vaccination reduced the risk of GISx, ANSx, and SNSx. Sequelae frequently ascribed to COVID-19 may manifest with similar or higher frequency after other infections, except ANSx.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141783382","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}
Abstract Background Spinal neurocysticercosis is a rare central nervous system infection caused by the larval form of the Taenia solium tapeworm. Due to its rarity, most knowledge is derived from isolated case reports. Objectives This systematic review aims to evaluate existing case reports and observational studies to provide a comprehensive overview of the disease's clinical presentation, and treatment outcomes. Methods Adhering to PRISMA guidelines, a search was conducted across multiple databases including PubMed, Scopus, Embase, and Google Scholar. Case reports, case series, and observational studies were included. The review is registered with PROSPERO (CRD42024496957). Results The search yielded 163 records describing 197 patients. Symptoms ranged from one week to over three years, with the most common being paraparesis or quadriparesis (61%) and back pain. Treatment modalities varied. with a combination of surgery and cysticidal drugs being the most preferred (45.2%) treatment. Surgery was done in 77% (152/197) of cases. In 45 % of cases (89/197) cysticidal drugs were given following surgery. Medical treatment alone was given to 22% (43/197) of patients. The majority of cases (92%) irrespective of treatment modality showed clinical improvement. Post-operative complications caused three deaths. Conclusions We noted that surgery followed by cysticidal drugs was the most preferred treatment. Medical treatment alone was given to many patients. Clinical improvement was observed in most cases, regardless of the treatment option used. The use of cysticidal drugs could eliminate the need for surgery in many spinal neurocysticercosis patients.
{"title":"Treatment Outcome in Patients With Spinal Neurocysticercosis: A Systematic Review of Published Cases and Case Series","authors":"Ravindra Kumar Garg, Imran Rizvi, Harish Nigam, Shweta Pandey, Ravi Uniyal","doi":"10.1101/2024.07.24.24310906","DOIUrl":"https://doi.org/10.1101/2024.07.24.24310906","url":null,"abstract":"Abstract\u0000Background\u0000Spinal neurocysticercosis is a rare central nervous system infection caused by the larval form of the Taenia solium tapeworm. Due to its rarity, most knowledge is derived from isolated case reports. Objectives\u0000This systematic review aims to evaluate existing case reports and observational studies to provide a comprehensive overview of the disease's clinical presentation, and treatment outcomes. Methods\u0000Adhering to PRISMA guidelines, a search was conducted across multiple databases including PubMed, Scopus, Embase, and Google Scholar. Case reports, case series, and observational studies were included. The review is registered with PROSPERO (CRD42024496957). Results\u0000The search yielded 163 records describing 197 patients. Symptoms ranged from one week to over three years, with the most common being paraparesis or quadriparesis (61%) and back pain. Treatment modalities varied. with a combination of surgery and cysticidal drugs being the most preferred (45.2%) treatment. Surgery was done in 77% (152/197) of cases. In 45 % of cases (89/197) cysticidal drugs were given following surgery. Medical treatment alone was given to 22% (43/197) of patients. The majority of cases (92%) irrespective of treatment modality showed clinical improvement. Post-operative complications caused three deaths. Conclusions\u0000We noted that surgery followed by cysticidal drugs was the most preferred treatment. Medical treatment alone was given to many patients. Clinical improvement was observed in most cases, regardless of the treatment option used. The use of cysticidal drugs could eliminate the need for surgery in many spinal neurocysticercosis patients.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141783387","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 : 2024-07-26DOI: 10.1101/2024.07.25.24311016
Jeffrey P Townsend, Hayley B. Hassler, Alex Dornburg
COVID-19 booster vaccinations mitigate transmission and reduce the morbidity and mortality associated with infection. However, the optimal date for booster administration remains uncertain. Geographic variation in infection rates throughout the year make it challenging to intuit the best yearly booster administration date to effectively prevent infection, and also challenging to provide best guidance in how to alter booster administration in response to a breakthrough infection. Therefore, we leverage longitudinal antibody and reinfection probabilities with spatiotemporal projections of COVID-19 incidence to develop a geographically-informed approach to optimizing the timing of booster vaccination. Additionally, we assess the delay in booster vaccination that is warranted following breakthrough infections whenever they occur during the year, enabling an approach that acknowledges and respects diverse immune statuses, thereby addressing a substantial barrier to uptake. Our results provide guidance for individual decision-making and healthcare provider recommendations, as well as optimal public health policies.
{"title":"Optimal annual COVID-19 vaccine boosting dates following previous booster vaccination or breakthrough infection","authors":"Jeffrey P Townsend, Hayley B. Hassler, Alex Dornburg","doi":"10.1101/2024.07.25.24311016","DOIUrl":"https://doi.org/10.1101/2024.07.25.24311016","url":null,"abstract":"COVID-19 booster vaccinations mitigate transmission and reduce the morbidity and mortality associated with infection. However, the optimal date for booster administration remains uncertain. Geographic variation in infection rates throughout the year make it challenging to intuit the best yearly booster administration date to effectively prevent infection, and also challenging to provide best guidance in how to alter booster administration in response to a breakthrough infection. Therefore, we leverage longitudinal antibody and reinfection probabilities with spatiotemporal projections of COVID-19 incidence to develop a geographically-informed approach to optimizing the timing of booster vaccination. Additionally, we assess the delay in booster vaccination that is warranted following breakthrough infections whenever they occur during the year, enabling an approach that acknowledges and respects diverse immune statuses, thereby addressing a substantial barrier to uptake. Our results provide guidance for individual decision-making and healthcare provider recommendations, as well as optimal public health policies.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141783384","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 : 2024-07-25DOI: 10.1101/2024.07.25.24310969
Luz M. Moyano, Franco E. León-Jimenez, Nataly B.F. Mendoza-Farro, Adriana Montoya Reategui, Joel Emmanuel Inga-Chero, Karim Dioses Diaz, Moisés Barranzuela-Herrera, Sophia Cavalcanti Ramírez
Background: Effective dengue management enhances the chances of survival. The level of adherence to the suggestions in northern Peru is uncertain. The primary aim of the study was to assess adherence to the 2016 PAHO guideline on dengue in a hospital located in northern Peru during the period from 2022 to 2023. Methodology/principal findings: The study performed a cross-sectional design and exploratory analysis, reviewing 141 medical records. Fifty-four percent were from 2023; 65.9% were from women; 46.1% came from another healthcare center; 76.6% had diagnosis of dengue with warning signs; 20.7% had severe dengue; and 18.44% died. We found at least one error in the classification of severity and/or treatment in non-hospital healthcare facilities (91.5%), triage (88.5%), and uviclin/observation (52.6%). Errors in classification and inadequate hydration in the non-hospital healthcare centers, triage, and uviclin/observation were: 35.8%/53.7%, 30.6%/76.6%, and 10.1%/45.6%, respectively. Persistent errors were inadequate hydration in triage (76.86%) and urinary flow in the center (73.13%). In a bivariate analysis, mortality was associated with older age (p = 0.035), having a case from 2023 (p = 0.0073), having a case from the study hospital (p = 0.083), and having severe dengue (p<0.001). In the multivariate analysis, only severe dengue (OR 318.4, 95% IC [33.8-2996], p<0.001) was associated with mortality. Conclusions/significance: We found a high frequency of misclassification and management errors in these three scenarios, but they were not associated with higher mortality.
{"title":"Adherence to the 2016 PAHO Clinical Practice Guideline on Dengue in a Hospital in Northern Peru, 2022-2023","authors":"Luz M. Moyano, Franco E. León-Jimenez, Nataly B.F. Mendoza-Farro, Adriana Montoya Reategui, Joel Emmanuel Inga-Chero, Karim Dioses Diaz, Moisés Barranzuela-Herrera, Sophia Cavalcanti Ramírez","doi":"10.1101/2024.07.25.24310969","DOIUrl":"https://doi.org/10.1101/2024.07.25.24310969","url":null,"abstract":"Background: Effective dengue management enhances the chances of survival. The level of adherence to the suggestions in northern Peru is uncertain. The primary aim of the study was to assess adherence to the 2016 PAHO guideline on dengue in a hospital located in northern Peru during the period from 2022 to 2023. Methodology/principal findings: The study performed a cross-sectional design and exploratory analysis, reviewing 141 medical records. Fifty-four percent were from 2023; 65.9% were from women; 46.1% came from another healthcare center; 76.6% had diagnosis of dengue with warning signs; 20.7% had severe dengue; and 18.44% died. We found at least one error in the classification of severity and/or treatment in non-hospital healthcare facilities (91.5%), triage (88.5%), and uviclin/observation (52.6%). Errors in classification and inadequate hydration in the non-hospital healthcare centers, triage, and uviclin/observation were: 35.8%/53.7%, 30.6%/76.6%, and 10.1%/45.6%, respectively. Persistent errors were inadequate hydration in triage (76.86%) and urinary flow in the center (73.13%). In a bivariate analysis, mortality was associated with older age (p = 0.035), having a case from 2023 (p = 0.0073), having a case from the study hospital (p = 0.083), and having severe dengue (p<0.001). In the multivariate analysis, only severe dengue (OR 318.4, 95% IC [33.8-2996], p<0.001) was associated with mortality. Conclusions/significance: We found a high frequency of misclassification and management errors in these three scenarios, but they were not associated with higher mortality.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141783388","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 : 2024-07-25DOI: 10.1101/2024.07.24.24310954
Nadia mazarakis, Zheng Quan Toh, Jill Nguyen, Rachel Higgins, James Rudge, Belinda Whittle, Nicholas J. Woudberg, Justin Devine, Andrew Gooley, Florian Lapierre, Nigel W. Crawford, Shidan Tosif, Paul Licciardi
Serological surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies is important to monitor population COVID-19 immunity. Dried blood spots (DBS) are a valuable method for serosurveys, particularly in remote settings and in children. We compared the measurement of SARS-CoV-2 spike-specific IgG in paired blood samples collected by standard venepuncture (serum) and the hemaPEN microsampling DBS device from children and adults using an established in-house ELISA. A total of 83 participants (10 months to 65 years of age) with paired serum and hemapen samples were included in the analysis; N=41 adults (36 COVID-positive and 5 COVID-negative) and N=42 children (37 COVID positive and 5 COVID-negative). Moderate- to strong-correlations between paired hemaPEN DBS eluates and serum SARS-CoV-2 IgG antibodies for RBD (r=0.9472, P<.0001) and S1 proteins (r=0.6892, P<.0001) were found. Similar results were observed in both adult and paediatric populations. SARS-CoV-2 spike-specific IgG in hemaPEN DBS samples remained stable for at least 35 weeks at room temperature. HemaPEN samples showed high specificity and sensitivity (100% and 89.89%, respectively) compared with serum. The use of the microsampling hemaPEN device for DBS sample collection is a feasible approach for assessing SARS-CoV-2 antibodies for serosurveillance studies, particularly in remote settings and in children.
{"title":"Evaluation of SARS-CoV-2 antibody response between paired fingerprick (hemaPEN) and venepuncture collected samples in children and adults","authors":"Nadia mazarakis, Zheng Quan Toh, Jill Nguyen, Rachel Higgins, James Rudge, Belinda Whittle, Nicholas J. Woudberg, Justin Devine, Andrew Gooley, Florian Lapierre, Nigel W. Crawford, Shidan Tosif, Paul Licciardi","doi":"10.1101/2024.07.24.24310954","DOIUrl":"https://doi.org/10.1101/2024.07.24.24310954","url":null,"abstract":"Serological surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies is important to monitor population COVID-19 immunity. Dried blood spots (DBS) are a valuable method for serosurveys, particularly in remote settings and in children. We compared the measurement of SARS-CoV-2 spike-specific IgG in paired blood samples collected by standard venepuncture (serum) and the hemaPEN microsampling DBS device from children and adults using an established in-house ELISA. A total of 83 participants (10 months to 65 years of age) with paired serum and hemapen samples were included in the analysis; N=41 adults (36 COVID-positive and 5 COVID-negative) and N=42 children (37 COVID positive and 5 COVID-negative). Moderate- to strong-correlations between paired hemaPEN DBS eluates and serum SARS-CoV-2 IgG antibodies for RBD (r=0.9472, P<.0001) and S1 proteins (r=0.6892, P<.0001) were found. Similar results were observed in both adult and paediatric populations. SARS-CoV-2 spike-specific IgG in hemaPEN DBS samples remained stable for at least 35 weeks at room temperature. HemaPEN samples showed high specificity and sensitivity (100% and 89.89%, respectively) compared with serum. The use of the microsampling hemaPEN device for DBS sample collection is a feasible approach for assessing SARS-CoV-2 antibodies for serosurveillance studies, particularly in remote settings and in children.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141783423","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 : 2024-07-24DOI: 10.1101/2024.07.23.24310825
Tamiru Alkie, Neda Nasheri, Pablo Romero-Barrios, Angela Catford, Jay Krishnan, Lemarie Pama, Kathleen Hooper-McGrevy, Charles Nfon, Yohannes Berhane
Highly pathogenic avian influenza (HPAI) clade 2.3.4.4b H5Nx viruses continue to cause episodic incursions and have been detected in more than 12 taxonomic orders encompassing more than 80 avian species, land and marine mammals, including recent detections in dairy cattle. The HPAI H5N1 spillover to these important livestock species creates a new interface for human exposure and raises food safety concerns. Presence of H5N1 genetic material in one out of five retail pasteurized milk samples in the USA has prompted the evaluation of pasteurization processes for the inactivation of influenza viruses. Our study examined whether pasteurization could effectively inactivate HPAI H5N1 inoculated raw whole milk samples. We heated 1 mL of non-homogenized milk samples to attain an internal temperature of 63C or 72C and spiked with 6.3 log EID50 of clade 2.3.4.4b H5N1 virus. Complete inactivation was achieved after incubation of the H5N1 spiked raw milk at 63C for 30 minutes. In addition, complete viral inactivation was observed in seven out of eight replicates of raw milk samples treated at 72C for 15 seconds. In one replicate, a 4.56 log reduction was achieved, which is about 1 log higher than the average viral quantities detected in bulk tanks in affected areas. Therefore, we conclude that pasteurization of milk is an effective strategy for mitigation of risk of human exposure to milk contaminated with H5N1 virus.
{"title":"Effectiveness of Pasteurization for the Inactivation of H5N1 Influenza Virus in Raw Whole Milk","authors":"Tamiru Alkie, Neda Nasheri, Pablo Romero-Barrios, Angela Catford, Jay Krishnan, Lemarie Pama, Kathleen Hooper-McGrevy, Charles Nfon, Yohannes Berhane","doi":"10.1101/2024.07.23.24310825","DOIUrl":"https://doi.org/10.1101/2024.07.23.24310825","url":null,"abstract":"Highly pathogenic avian influenza (HPAI) clade 2.3.4.4b H5Nx viruses continue to cause episodic incursions and have been detected in more than 12 taxonomic orders encompassing more than 80 avian species, land and marine mammals, including recent detections in dairy cattle. The HPAI H5N1 spillover to these important livestock species creates a new interface for human exposure and raises food safety concerns. Presence of H5N1 genetic material in one out of five retail pasteurized milk samples in the USA has prompted the evaluation of pasteurization processes for the inactivation of influenza viruses. Our study examined whether pasteurization could effectively inactivate HPAI H5N1 inoculated raw whole milk samples. We heated 1 mL of non-homogenized milk samples to attain an internal temperature of 63C or 72C and spiked with 6.3 log EID50 of clade 2.3.4.4b H5N1 virus. Complete inactivation was achieved after incubation of the H5N1 spiked raw milk at 63C for 30 minutes. In addition, complete viral inactivation was observed in seven out of eight replicates of raw milk samples treated at 72C for 15 seconds. In one replicate, a 4.56 log reduction was achieved, which is about 1 log higher than the average viral quantities detected in bulk tanks in affected areas. Therefore, we conclude that pasteurization of milk is an effective strategy for mitigation of risk of human exposure to milk contaminated with H5N1 virus.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141785978","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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