Elin M Svensson, Sofiati Dian, Lindsey Te Brake, Ahmad Rizal Ganiem, Vycke Yunivita, Arjan van Laarhoven, Reinout Van Crevel, Rovina Ruslami, Rob E Aarnoutse
Background: Intensified antimicrobial treatment with higher rifampicin doses may improve outcome of tuberculous meningitis, but the desirable exposure and necessary dose are unknown. Our objective was to characterize the relationship between rifampicin exposures and mortality in order to identify optimal dosing for tuberculous meningitis.
Methods: An individual patient meta-analysis was performed on data from 3 Indonesian randomized controlled phase 2 trials comparing oral rifampicin 450 mg (~10 mg/kg) to intensified regimens including 750-1350 mg orally, or a 600-mg intravenous infusion. Pharmacokinetic data from plasma and cerebrospinal fluid (CSF) were analyzed with nonlinear mixed-effects modeling. Six-month survival was described with parametric time-to-event models.
Results: Pharmacokinetic analyses included 133 individuals (1150 concentration measurements, 170 from CSF). The final model featured 2 disposition compartments, saturable clearance, and autoinduction. Rifampicin CSF concentrations were described by a partition coefficient (5.5%; 95% confidence interval [CI], 4.5%-6.4%) and half-life for distribution plasma to CSF (2.1 hours; 95% CI, 1.3-2.9 hours). Higher CSF protein concentration increased the partition coefficient. Survival of 148 individuals (58 died, 15 dropouts) was well described by an exponentially declining hazard, with lower age, higher baseline Glasgow Coma Scale score, and higher individual rifampicin plasma exposure reducing the hazard. Simulations predicted an increase in 6-month survival from approximately 50% to approximately 70% upon increasing the oral rifampicin dose from 10 to 30 mg/kg, and predicted that even higher doses would further improve survival.
Conclusions: Higher rifampicin exposure substantially decreased the risk of death, and the maximal effect was not reached within the studied range. We suggest a rifampicin dose of at least 30 mg/kg to be investigated in phase 3 clinical trials.
{"title":"Model-Based Meta-analysis of Rifampicin Exposure and Mortality in Indonesian Tuberculous Meningitis Trials.","authors":"Elin M Svensson, Sofiati Dian, Lindsey Te Brake, Ahmad Rizal Ganiem, Vycke Yunivita, Arjan van Laarhoven, Reinout Van Crevel, Rovina Ruslami, Rob E Aarnoutse","doi":"10.1093/cid/ciz1071","DOIUrl":"10.1093/cid/ciz1071","url":null,"abstract":"<p><strong>Background: </strong>Intensified antimicrobial treatment with higher rifampicin doses may improve outcome of tuberculous meningitis, but the desirable exposure and necessary dose are unknown. Our objective was to characterize the relationship between rifampicin exposures and mortality in order to identify optimal dosing for tuberculous meningitis.</p><p><strong>Methods: </strong>An individual patient meta-analysis was performed on data from 3 Indonesian randomized controlled phase 2 trials comparing oral rifampicin 450 mg (~10 mg/kg) to intensified regimens including 750-1350 mg orally, or a 600-mg intravenous infusion. Pharmacokinetic data from plasma and cerebrospinal fluid (CSF) were analyzed with nonlinear mixed-effects modeling. Six-month survival was described with parametric time-to-event models.</p><p><strong>Results: </strong>Pharmacokinetic analyses included 133 individuals (1150 concentration measurements, 170 from CSF). The final model featured 2 disposition compartments, saturable clearance, and autoinduction. Rifampicin CSF concentrations were described by a partition coefficient (5.5%; 95% confidence interval [CI], 4.5%-6.4%) and half-life for distribution plasma to CSF (2.1 hours; 95% CI, 1.3-2.9 hours). Higher CSF protein concentration increased the partition coefficient. Survival of 148 individuals (58 died, 15 dropouts) was well described by an exponentially declining hazard, with lower age, higher baseline Glasgow Coma Scale score, and higher individual rifampicin plasma exposure reducing the hazard. Simulations predicted an increase in 6-month survival from approximately 50% to approximately 70% upon increasing the oral rifampicin dose from 10 to 30 mg/kg, and predicted that even higher doses would further improve survival.</p><p><strong>Conclusions: </strong>Higher rifampicin exposure substantially decreased the risk of death, and the maximal effect was not reached within the studied range. We suggest a rifampicin dose of at least 30 mg/kg to be investigated in phase 3 clinical trials.</p>","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/cid/ciz1071","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74103053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mikaela Smit, Pablo N Perez-Guzman, Kennedy K Mutai, Rachel Cassidy, Joseph Kibachio, Nduku Kilonzo, Timothy B Hallett
Background: The noncommunicable disease (NCD) burden in Kenya is not well characterized, despite estimates needed to identify future health priorities. We aimed to quantify current and future NCD burden in Kenya by human immunodeficiency virus (HIV) status.
Methods: Original systematic reviews and meta-analyses of prevalence/incidence of cardiovascular disease (CVD), chronic kidney disease, depression, diabetes, high total cholesterol, hypertension, human papillomavirus infection, and related precancerous stages in Kenya were carried out. An individual-based model was developed, simulating births, deaths, HIV disease and treatment, aforementioned NCDs, and cancers. The model was parameterized using systematic reviews and epidemiological national and regional surveillance data. NCD burden was quantified for 2018-2035 by HIV status among adults.
Results: Systematic reviews identified prevalence/incidence data for each NCD except ischemic heart disease. The model estimates that 51% of Kenyan adults currently suffer from ≥1 NCD, with a higher burden in people living with HIV (PLWH) compared to persons not living with HIV (62% vs 51%), driven by their higher age profile and partly by HIV-related risk for NCDs. Hypertension and high total cholesterol are the main NCD drivers (adult prevalence of 20.5% [5.3 million] and 9.0% [2.3 million]), with CVD and cancers the main causes of death. The burden is projected to increase by 2035 (56% in persons not living with HIV; 71% in PLWH), with population growth doubling the number of people needing services (15.4 million to 28.1 million) by 2035.
Conclusions: NCD services will need to be expanded in Kenya. Guidelines in Kenya already support provision of these among both the general and populations living with HIV; however, coverage remains low.
{"title":"Mapping the Current and Future Noncommunicable Disease Burden in Kenya by Human Immunodeficiency Virus Status: A Modeling Study.","authors":"Mikaela Smit, Pablo N Perez-Guzman, Kennedy K Mutai, Rachel Cassidy, Joseph Kibachio, Nduku Kilonzo, Timothy B Hallett","doi":"10.1093/cid/ciz1103","DOIUrl":"10.1093/cid/ciz1103","url":null,"abstract":"<p><strong>Background: </strong>The noncommunicable disease (NCD) burden in Kenya is not well characterized, despite estimates needed to identify future health priorities. We aimed to quantify current and future NCD burden in Kenya by human immunodeficiency virus (HIV) status.</p><p><strong>Methods: </strong>Original systematic reviews and meta-analyses of prevalence/incidence of cardiovascular disease (CVD), chronic kidney disease, depression, diabetes, high total cholesterol, hypertension, human papillomavirus infection, and related precancerous stages in Kenya were carried out. An individual-based model was developed, simulating births, deaths, HIV disease and treatment, aforementioned NCDs, and cancers. The model was parameterized using systematic reviews and epidemiological national and regional surveillance data. NCD burden was quantified for 2018-2035 by HIV status among adults.</p><p><strong>Results: </strong>Systematic reviews identified prevalence/incidence data for each NCD except ischemic heart disease. The model estimates that 51% of Kenyan adults currently suffer from ≥1 NCD, with a higher burden in people living with HIV (PLWH) compared to persons not living with HIV (62% vs 51%), driven by their higher age profile and partly by HIV-related risk for NCDs. Hypertension and high total cholesterol are the main NCD drivers (adult prevalence of 20.5% [5.3 million] and 9.0% [2.3 million]), with CVD and cancers the main causes of death. The burden is projected to increase by 2035 (56% in persons not living with HIV; 71% in PLWH), with population growth doubling the number of people needing services (15.4 million to 28.1 million) by 2035.</p><p><strong>Conclusions: </strong>NCD services will need to be expanded in Kenya. Guidelines in Kenya already support provision of these among both the general and populations living with HIV; however, coverage remains low.</p>","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79674316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Noncommunicable Diseases: Yet Another Challenge for Human Immunodeficiency Virus Treatment and Care in Sub-Saharan Africa.","authors":"Brian K Agan, Vincent C Marconi","doi":"10.1093/cid/ciz1104","DOIUrl":"10.1093/cid/ciz1104","url":null,"abstract":"","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88188347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jun Li, C. Armon, F. Palella, R. Novak, D. Ward, S. Purinton, M. Durham, K. Buchacz
BACKGROUND Although chlamydia (CT) and gonorrhea (GC) infections are increasing in the United States, there are limited data on their incidence, testing rates and associated risk factors among persons with HIV (PWH), including by anatomic site among men who have sex with men (MSM). METHODS We analyzed 2007-2017 medical record data from HIV Outpatient Study participants in care at nine HIV clinics. We calculated CT (and GC) incidence and testing rates and assessed associations with sociodemographic and clinical factors using log-linear regression. RESULTS Among 4,727 PWH, 397 had 881 CT infections and 331 had 861 GC infections, with incidence of 2.95 and 2.88 per 100 person-years, respectively. From 2007-2017, incidence and testing rates increased by approximately 3.0- and 1.9-fold for CT and GC, respectively. Multivariable factors associated with incident CT (GC) included younger age, MSM, and prior diagnoses of sexually transmitted diseases (STDs). Among 1,159 MSM, 583 (50.3%) had 844 CT and 843 GC tests during 2016-2017, and 26.6% of tests were 3-site (urethra, rectum, and pharynx), yielding the highest rates of CT (GC) detection. Multivariable factors associated with CT (GC) testing included younger age, non-Hispanic/Latino black race, and having prior STDs. CONCLUSIONS Recent CT and GC incidence and testing increased among PWH; however, only half of MSM were tested for CT or GC during 2016-2017 and < 1/3 of tests were 3-site. To promote sexual health and STD prevention among PWH, including MSM, research regarding the added value of CT and GC testing across three anatomic sites is needed.
{"title":"Chlamydia and Gonorrhea Incidence and Testing among Patients in the HIV Outpatient Study, 2007-2017.","authors":"Jun Li, C. Armon, F. Palella, R. Novak, D. Ward, S. Purinton, M. Durham, K. Buchacz","doi":"10.1093/cid/ciz1085","DOIUrl":"https://doi.org/10.1093/cid/ciz1085","url":null,"abstract":"BACKGROUND\u0000Although chlamydia (CT) and gonorrhea (GC) infections are increasing in the United States, there are limited data on their incidence, testing rates and associated risk factors among persons with HIV (PWH), including by anatomic site among men who have sex with men (MSM).\u0000\u0000\u0000METHODS\u0000We analyzed 2007-2017 medical record data from HIV Outpatient Study participants in care at nine HIV clinics. We calculated CT (and GC) incidence and testing rates and assessed associations with sociodemographic and clinical factors using log-linear regression.\u0000\u0000\u0000RESULTS\u0000Among 4,727 PWH, 397 had 881 CT infections and 331 had 861 GC infections, with incidence of 2.95 and 2.88 per 100 person-years, respectively. From 2007-2017, incidence and testing rates increased by approximately 3.0- and 1.9-fold for CT and GC, respectively. Multivariable factors associated with incident CT (GC) included younger age, MSM, and prior diagnoses of sexually transmitted diseases (STDs). Among 1,159 MSM, 583 (50.3%) had 844 CT and 843 GC tests during 2016-2017, and 26.6% of tests were 3-site (urethra, rectum, and pharynx), yielding the highest rates of CT (GC) detection. Multivariable factors associated with CT (GC) testing included younger age, non-Hispanic/Latino black race, and having prior STDs.\u0000\u0000\u0000CONCLUSIONS\u0000Recent CT and GC incidence and testing increased among PWH; however, only half of MSM were tested for CT or GC during 2016-2017 and < 1/3 of tests were 3-site. To promote sexual health and STD prevention among PWH, including MSM, research regarding the added value of CT and GC testing across three anatomic sites is needed.","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79212743","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}
F. Schaltz-Buchholzer, M. Bjerregaard-Andersen, C. B. Øland, C. Golding, Elise Brenno Stjernholm, I. Monteiro, P. Aaby, C. Benn
BACKGROUND Bacille Calmette-Guérin (BCG) vaccination remains a cornerstone against tuberculosis. Randomized controlled trials (RCTs) has demonstrated that BCG-Denmark lowers all-cause mortality, but a recent RCT found no effect of BCG-Russia. Observational studies indicate that the genetically divergent BCG strains have different effects. METHODS Parallel-group, open-label RCT conducted at the National Hospital in Guinea-Bissau. Healthy neonates were randomized 1:1 to BCG-Denmark (2,851 randomized, 2,840 analyzed) versus BCG-Russia (2,845 randomized, 2,837 analyzed). We hypothesized that BCG-Denmark would reduce morbidity (primary outcome) and mortality while inducing more BCG reactions and Purified Protein Derivative (PPD) responses (secondary outcomes). Halfway through the trial, production of BCG-Denmark was halted, and the trial continued comparing BCG-Japan (3,191 neonates randomized, 3,184 analyzed) with BCG-Russia (3,170 randomized, 3,160 analyzed). Mortality and morbidity data were collected by telephone, at home-visits and at the National Hospital and assessed in Cox-models providing 6-week Mortality Rate Ratios (MRRs) and hospitalization Incidence Rate Ratios (IRRs). RESULTS By age 6 weeks, there were 140 admissions among neonates vaccinated with BCG-Denmark and 130 admissions for BCG-Russia, IRR=1.08 (95% Confidence Interval: 0.84-1.37). For BCG-Japan there were 185 admissions versus 161 admissions for BCG-Russia, IRR=1.15 (0.93-1.43). The 6-week mortality did not differ, BCG-Denmark/BCG-Russia MRR=1.15 (0.74-1.81); BCG-Japan/BCG-Russia MRR=0.71 (0.43-1.19). BCG-Denmark and BCG-Japan induced more BCG scars and PPD reactions than BCG-Russia. CONCLUSION BCG strains did not affect morbidity. BCG-Denmark and BCG-Japan were more immunogenic than BCG-Russia by the measures traditionally viewed as surrogates for successful immunization. The implications of strain differences for tuberculosis protection and overall health warrant further study.
{"title":"Early vaccination with BCG-Denmark or BCG-Japan versus BCG-Russia to healthy newborns in Guinea-Bissau: A randomized controlled trial.","authors":"F. Schaltz-Buchholzer, M. Bjerregaard-Andersen, C. B. Øland, C. Golding, Elise Brenno Stjernholm, I. Monteiro, P. Aaby, C. Benn","doi":"10.1093/cid/ciz1080","DOIUrl":"https://doi.org/10.1093/cid/ciz1080","url":null,"abstract":"BACKGROUND\u0000Bacille Calmette-Guérin (BCG) vaccination remains a cornerstone against tuberculosis. Randomized controlled trials (RCTs) has demonstrated that BCG-Denmark lowers all-cause mortality, but a recent RCT found no effect of BCG-Russia. Observational studies indicate that the genetically divergent BCG strains have different effects.\u0000\u0000\u0000METHODS\u0000Parallel-group, open-label RCT conducted at the National Hospital in Guinea-Bissau. Healthy neonates were randomized 1:1 to BCG-Denmark (2,851 randomized, 2,840 analyzed) versus BCG-Russia (2,845 randomized, 2,837 analyzed). We hypothesized that BCG-Denmark would reduce morbidity (primary outcome) and mortality while inducing more BCG reactions and Purified Protein Derivative (PPD) responses (secondary outcomes). Halfway through the trial, production of BCG-Denmark was halted, and the trial continued comparing BCG-Japan (3,191 neonates randomized, 3,184 analyzed) with BCG-Russia (3,170 randomized, 3,160 analyzed). Mortality and morbidity data were collected by telephone, at home-visits and at the National Hospital and assessed in Cox-models providing 6-week Mortality Rate Ratios (MRRs) and hospitalization Incidence Rate Ratios (IRRs).\u0000\u0000\u0000RESULTS\u0000By age 6 weeks, there were 140 admissions among neonates vaccinated with BCG-Denmark and 130 admissions for BCG-Russia, IRR=1.08 (95% Confidence Interval: 0.84-1.37). For BCG-Japan there were 185 admissions versus 161 admissions for BCG-Russia, IRR=1.15 (0.93-1.43). The 6-week mortality did not differ, BCG-Denmark/BCG-Russia MRR=1.15 (0.74-1.81); BCG-Japan/BCG-Russia MRR=0.71 (0.43-1.19). BCG-Denmark and BCG-Japan induced more BCG scars and PPD reactions than BCG-Russia.\u0000\u0000\u0000CONCLUSION\u0000BCG strains did not affect morbidity. BCG-Denmark and BCG-Japan were more immunogenic than BCG-Russia by the measures traditionally viewed as surrogates for successful immunization. The implications of strain differences for tuberculosis protection and overall health warrant further study.","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91434831","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}
G. van den Bunt, A. Fluit, M. Bootsma, E. V. Duijkeren, J. Scharringa, W. Pelt, M. Bonten
BACKGROUND In the Netherlands the prevalence of intestinal Extended-spectrum Beta-lactamase producing Enterobacteriaceae (ESBL-E) carriage in community-dwelling subjects is ~5%. Little is known about the dynamics of ESBL-E carriage. METHODS In a nation-wide population-based study (2014-2016) with 4,177 community-dwelling subjects, fecal samples from 656 subjects were also collected after one (T=1) and six (T=2) months. Growth of ESBL-E was quantified and whole genome sequence analysis performed. Subjects were categorized as "incidental", "short-term", "long-term" carrier or as "non-carrier". Risk factors were determined by random forest models and logistic regression. Transmissibility and duration of ESBL-E carriage was quantified using a transmission model also using previous study data. RESULTS Out of 656 participants, 96 were ESBL-E carrier at T=0. Sixty-six (10.1%) subjects were "incidental carriers", 22 (3.3%) "short-term carriers", 38 (5.8%) "long-term carriers" and 530 (80.8%) "non-carrier". Risk factors for long-term carriage were travelling to Asia, swimming in sea/ocean, and not changing the kitchen towel daily. The log-transformed CFU ratio at T=0 was predictive for ESBL-E carriage at T=1 (OR: 1.3, 95%CI: 1.2-1.6) and T=2 (OR: 1.2, 95%CI: 1.1-1.4). Model simulations revealed a median decolonization rate of 2.83/year, an average duration of carriage of 0.35 years and an acquisition rate of 0.34/year. The trend of the acquisition rate during the study period was close to zero. CONCLUSION Risk factors for long-term ESBL-E carriage were travel and hygiene related . The dynamics of ESBL-E carriage in the general Dutch population are characterized by balancing decolonization and acquisition rates.
{"title":"Dynamics of intestinal carriage of Extended-spectrum Beta-lactamase producing Enterobacteriaceae in the Dutch general population (2014-2016).","authors":"G. van den Bunt, A. Fluit, M. Bootsma, E. V. Duijkeren, J. Scharringa, W. Pelt, M. Bonten","doi":"10.1093/cid/ciz1091","DOIUrl":"https://doi.org/10.1093/cid/ciz1091","url":null,"abstract":"BACKGROUND\u0000In the Netherlands the prevalence of intestinal Extended-spectrum Beta-lactamase producing Enterobacteriaceae (ESBL-E) carriage in community-dwelling subjects is ~5%. Little is known about the dynamics of ESBL-E carriage.\u0000\u0000\u0000METHODS\u0000In a nation-wide population-based study (2014-2016) with 4,177 community-dwelling subjects, fecal samples from 656 subjects were also collected after one (T=1) and six (T=2) months. Growth of ESBL-E was quantified and whole genome sequence analysis performed. Subjects were categorized as \"incidental\", \"short-term\", \"long-term\" carrier or as \"non-carrier\". Risk factors were determined by random forest models and logistic regression. Transmissibility and duration of ESBL-E carriage was quantified using a transmission model also using previous study data.\u0000\u0000\u0000RESULTS\u0000Out of 656 participants, 96 were ESBL-E carrier at T=0. Sixty-six (10.1%) subjects were \"incidental carriers\", 22 (3.3%) \"short-term carriers\", 38 (5.8%) \"long-term carriers\" and 530 (80.8%) \"non-carrier\". Risk factors for long-term carriage were travelling to Asia, swimming in sea/ocean, and not changing the kitchen towel daily. The log-transformed CFU ratio at T=0 was predictive for ESBL-E carriage at T=1 (OR: 1.3, 95%CI: 1.2-1.6) and T=2 (OR: 1.2, 95%CI: 1.1-1.4). Model simulations revealed a median decolonization rate of 2.83/year, an average duration of carriage of 0.35 years and an acquisition rate of 0.34/year. The trend of the acquisition rate during the study period was close to zero.\u0000\u0000\u0000CONCLUSION\u0000Risk factors for long-term ESBL-E carriage were travel and hygiene related . The dynamics of ESBL-E carriage in the general Dutch population are characterized by balancing decolonization and acquisition rates.","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77989690","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}
Lyndsay Bottichio, Amelia Keaton, Deepam Thomas, Tara Fulton, Amanda Tiffany, Anna Frick, Mia Mattioli, Amy Kahler, Jennifer Murphy, Mark Otto, Adiam Tesfai, Angela Fields, Kelly Kline, Jennifer Fiddner, Jeffrey Higa, Amber Barnes, Francine Arroyo, Annabelle Salvatierra, April Holland, Wendy Taylor, June Nash, Bozena M Morawski, Sarah Correll, Rachel Hinnenkamp, Jeffrey Havens, Kane Patel, Morgan N Schroeder, Lori Gladney, Haley Martin, Laura Whitlock, Natasha Dowell, Corinne Newhart, Louise Francois Watkins, Vincent Hill, Susan Lance, Stic Harris, Matthew Wise, Ian Williams, Colin Basler, Laura Gieraltowski
Background: Produce-associated outbreaks of Shiga toxin-producing Escherichia coli (STEC) were first identified in 1991. In April 2018, New Jersey and Pennsylvania officials reported a cluster of STEC O157 infections associated with multiple locations of a restaurant chain. The Centers for Disease Control and Prevention (CDC) queried PulseNet, the national laboratory network for foodborne disease surveillance, for additional cases and began a national investigation.
Methods: A case was defined as an infection between 13 March and 22 August 2018 with 1 of the 22 identified outbreak-associated E. coli O157:H7 or E. coli O61 pulsed-field gel electrophoresis pattern combinations, or with a strain STEC O157 that was closely related to the main outbreak strain by whole-genome sequencing. We conducted epidemiologic and traceback investigations to identify illness subclusters and common sources. A US Food and Drug Administration-led environmental assessment, which tested water, soil, manure, compost, and scat samples, was conducted to evaluate potential sources of STEC contamination.
Results: We identified 240 case-patients from 37 states; 104 were hospitalized, 28 developed hemolytic uremic syndrome, and 5 died. Of 179 people who were interviewed, 152 (85%) reported consuming romaine lettuce in the week before illness onset. Twenty subclusters were identified. Product traceback from subcluster restaurants identified numerous romaine lettuce distributors and growers; all lettuce originated from the Yuma growing region. Water samples collected from an irrigation canal in the region yielded the outbreak strain of STEC O157.
Conclusions: We report on the largest multistate leafy greens-linked STEC O157 outbreak in several decades. The investigation highlights the complexities associated with investigating outbreaks involving widespread environmental contamination.
{"title":"Shiga Toxin-Producing Escherichia coli Infections Associated With Romaine Lettuce-United States, 2018.","authors":"Lyndsay Bottichio, Amelia Keaton, Deepam Thomas, Tara Fulton, Amanda Tiffany, Anna Frick, Mia Mattioli, Amy Kahler, Jennifer Murphy, Mark Otto, Adiam Tesfai, Angela Fields, Kelly Kline, Jennifer Fiddner, Jeffrey Higa, Amber Barnes, Francine Arroyo, Annabelle Salvatierra, April Holland, Wendy Taylor, June Nash, Bozena M Morawski, Sarah Correll, Rachel Hinnenkamp, Jeffrey Havens, Kane Patel, Morgan N Schroeder, Lori Gladney, Haley Martin, Laura Whitlock, Natasha Dowell, Corinne Newhart, Louise Francois Watkins, Vincent Hill, Susan Lance, Stic Harris, Matthew Wise, Ian Williams, Colin Basler, Laura Gieraltowski","doi":"10.1093/cid/ciz1182","DOIUrl":"10.1093/cid/ciz1182","url":null,"abstract":"<p><strong>Background: </strong>Produce-associated outbreaks of Shiga toxin-producing Escherichia coli (STEC) were first identified in 1991. In April 2018, New Jersey and Pennsylvania officials reported a cluster of STEC O157 infections associated with multiple locations of a restaurant chain. The Centers for Disease Control and Prevention (CDC) queried PulseNet, the national laboratory network for foodborne disease surveillance, for additional cases and began a national investigation.</p><p><strong>Methods: </strong>A case was defined as an infection between 13 March and 22 August 2018 with 1 of the 22 identified outbreak-associated E. coli O157:H7 or E. coli O61 pulsed-field gel electrophoresis pattern combinations, or with a strain STEC O157 that was closely related to the main outbreak strain by whole-genome sequencing. We conducted epidemiologic and traceback investigations to identify illness subclusters and common sources. A US Food and Drug Administration-led environmental assessment, which tested water, soil, manure, compost, and scat samples, was conducted to evaluate potential sources of STEC contamination.</p><p><strong>Results: </strong>We identified 240 case-patients from 37 states; 104 were hospitalized, 28 developed hemolytic uremic syndrome, and 5 died. Of 179 people who were interviewed, 152 (85%) reported consuming romaine lettuce in the week before illness onset. Twenty subclusters were identified. Product traceback from subcluster restaurants identified numerous romaine lettuce distributors and growers; all lettuce originated from the Yuma growing region. Water samples collected from an irrigation canal in the region yielded the outbreak strain of STEC O157.</p><p><strong>Conclusions: </strong>We report on the largest multistate leafy greens-linked STEC O157 outbreak in several decades. The investigation highlights the complexities associated with investigating outbreaks involving widespread environmental contamination.</p>","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10982825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78085390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K. Ellingson, K. Pogreba-Brown, C. Gerba, S. Elliott
BACKGROUND Approximately 1 in 25 people admitted to a hospital in the United States will suffer a healthcare-associated infection (HAI). Environmental contamination of hospital surfaces contributes to HAI transmission. We investigated the impact of an antimicrobial surface coating on HAIs and environmental bioburden at two urban hospitals. METHODS A transparent antimicrobial surface coating was applied to patient rooms and common areas in three units at each hospital. Longitudinal regression models were used to compare changes in hospital-onset multidrug-resistant organism bloodstream infection (MDRO-BSI) and Clostridium difficile infection (CDI) rates in the 12 months before and after application of the surface coating. Incidence rate ratios (IRRs) were compared for units receiving the surface coating application and for contemporaneous control units. Environmental samples were collected pre- and post-application to identify bacterial colony forming units (CFU) and percent of sites positive for select clinically relevant pathogens. RESULTS Across both hospitals, there was a 36% decline in pooled HAIs (MDRO-BSI + CDI) in units receiving surface coating application (IRR=0.64, 95% CI=0.44-0.91), and no decline in control units (IRR=1.20, 95% CI=0.92-1.55). Following the surface application, total bacterial CFU at Hospitals A and B declined by 64% and 75%, respectively; the percentage of environmental samples positive for clinically relevant pathogens also declined significantly for both hospitals. CONCLUSIONS Statistically significant reductions in HAIs and environmental bioburden occurred in units receiving the antimicrobial surface coating, suggesting the potential for improved patient outcomes and persistent reduction in environmental contamination. Future studies should assess optimal implementation methods and long-term impact.
{"title":"Impact of a Novel Antimicrobial Surface Coating on Healthcare-Associated Infections and Environmental Bioburden at Two Urban Hospitals.","authors":"K. Ellingson, K. Pogreba-Brown, C. Gerba, S. Elliott","doi":"10.1093/cid/ciz1077","DOIUrl":"https://doi.org/10.1093/cid/ciz1077","url":null,"abstract":"BACKGROUND\u0000Approximately 1 in 25 people admitted to a hospital in the United States will suffer a healthcare-associated infection (HAI). Environmental contamination of hospital surfaces contributes to HAI transmission. We investigated the impact of an antimicrobial surface coating on HAIs and environmental bioburden at two urban hospitals.\u0000\u0000\u0000METHODS\u0000A transparent antimicrobial surface coating was applied to patient rooms and common areas in three units at each hospital. Longitudinal regression models were used to compare changes in hospital-onset multidrug-resistant organism bloodstream infection (MDRO-BSI) and Clostridium difficile infection (CDI) rates in the 12 months before and after application of the surface coating. Incidence rate ratios (IRRs) were compared for units receiving the surface coating application and for contemporaneous control units. Environmental samples were collected pre- and post-application to identify bacterial colony forming units (CFU) and percent of sites positive for select clinically relevant pathogens.\u0000\u0000\u0000RESULTS\u0000Across both hospitals, there was a 36% decline in pooled HAIs (MDRO-BSI + CDI) in units receiving surface coating application (IRR=0.64, 95% CI=0.44-0.91), and no decline in control units (IRR=1.20, 95% CI=0.92-1.55). Following the surface application, total bacterial CFU at Hospitals A and B declined by 64% and 75%, respectively; the percentage of environmental samples positive for clinically relevant pathogens also declined significantly for both hospitals.\u0000\u0000\u0000CONCLUSIONS\u0000Statistically significant reductions in HAIs and environmental bioburden occurred in units receiving the antimicrobial surface coating, suggesting the potential for improved patient outcomes and persistent reduction in environmental contamination. Future studies should assess optimal implementation methods and long-term impact.","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78383697","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}
{"title":"How much impact do antimicrobial surfaces really have on healthcare-acquired infection?","authors":"S. Dancer","doi":"10.1093/cid/ciz1078","DOIUrl":"https://doi.org/10.1093/cid/ciz1078","url":null,"abstract":"","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86258484","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 : 2020-11-04DOI: 10.1101/2020.11.02.20224824
S. Lumley, Jia Wei, D. O’Donnell, N. Stoesser, P. Matthews, A. Howarth, S. Hatch, B. Marsden, S. Cox, T. James, Liam J. Peck, Thomas G Ritter, Z. de Toledo, R. Cornall, E. Jones, D. Stuart, G. Screaton, Daniela Ebner, S. Hoosdally, D. Crook, C. Conlon, K. Pouwels, A. Walker, T. Peto, T. Walker, K. Jeffery, D. Eyre
Background SARS-CoV-2 IgG antibody measurements can be used to estimate the proportion of a population exposed or infected and may be informative about the risk of future infection. Previous estimates of the duration of antibody responses vary. Methods We present 6 months of data from a longitudinal seroprevalence study of 3217 UK healthcare workers (HCWs). Serial measurements of IgG antibodies to SARS-CoV-2 nucleocapsid were obtained. Bayesian mixed linear models were used to investigate antibody waning and associations with age, gender, ethnicity, previous symptoms and PCR results. Results In this cohort of working age HCWs, antibody levels rose to a peak at 24 (95% credibility interval, CrI 19-31) days post-first positive PCR test, before beginning to fall. Considering 452 IgG seropositive HCWs over a median of 121 days (maximum 171 days) from their maximum positive IgG titre, the mean estimated antibody half-life was 85 (95%CrI, 81-90) days. The estimated mean time to loss of a positive antibody result was 137 (95%CrI 127-148) days. We observed variation between individuals; higher maximum observed IgG titres were associated with longer estimated antibody half-lives. Increasing age, Asian ethnicity and prior self-reported symptoms were independently associated with higher maximum antibody levels, and increasing age and a positive PCR test undertaken for symptoms with longer antibody half-lives. Conclusion IgG antibody levels to SARS-CoV-2 nucleocapsid wane within months, and faster in younger adults and those without symptoms. Ongoing longitudinal studies are required to track the long-term duration of antibody levels and their association with immunity to SARS-CoV-2 reinfection.
{"title":"The duration, dynamics and determinants of SARS-CoV-2 antibody responses in individual healthcare workers","authors":"S. Lumley, Jia Wei, D. O’Donnell, N. Stoesser, P. Matthews, A. Howarth, S. Hatch, B. Marsden, S. Cox, T. James, Liam J. Peck, Thomas G Ritter, Z. de Toledo, R. Cornall, E. Jones, D. Stuart, G. Screaton, Daniela Ebner, S. Hoosdally, D. Crook, C. Conlon, K. Pouwels, A. Walker, T. Peto, T. Walker, K. Jeffery, D. Eyre","doi":"10.1101/2020.11.02.20224824","DOIUrl":"https://doi.org/10.1101/2020.11.02.20224824","url":null,"abstract":"Background SARS-CoV-2 IgG antibody measurements can be used to estimate the proportion of a population exposed or infected and may be informative about the risk of future infection. Previous estimates of the duration of antibody responses vary. Methods We present 6 months of data from a longitudinal seroprevalence study of 3217 UK healthcare workers (HCWs). Serial measurements of IgG antibodies to SARS-CoV-2 nucleocapsid were obtained. Bayesian mixed linear models were used to investigate antibody waning and associations with age, gender, ethnicity, previous symptoms and PCR results. Results In this cohort of working age HCWs, antibody levels rose to a peak at 24 (95% credibility interval, CrI 19-31) days post-first positive PCR test, before beginning to fall. Considering 452 IgG seropositive HCWs over a median of 121 days (maximum 171 days) from their maximum positive IgG titre, the mean estimated antibody half-life was 85 (95%CrI, 81-90) days. The estimated mean time to loss of a positive antibody result was 137 (95%CrI 127-148) days. We observed variation between individuals; higher maximum observed IgG titres were associated with longer estimated antibody half-lives. Increasing age, Asian ethnicity and prior self-reported symptoms were independently associated with higher maximum antibody levels, and increasing age and a positive PCR test undertaken for symptoms with longer antibody half-lives. Conclusion IgG antibody levels to SARS-CoV-2 nucleocapsid wane within months, and faster in younger adults and those without symptoms. Ongoing longitudinal studies are required to track the long-term duration of antibody levels and their association with immunity to SARS-CoV-2 reinfection.","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81547785","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}