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Background Data on the true prevalence of respiratory syncytial virus (RSV) among medically attended acute respiratory illnesses (MAARI) has been limited by the lack of regular clinical testing of mild to moderate illnesses. Here we present a prospective evaluation of the epidemiology of RSV-associated MAARI across age groups and multimorbidity status over 3 seasons, which is informative in light of the recommendations for shared decision making for vaccination in older adults. Methods Ambulatory patients ≥6 months of age meeting a common MAARI case definition were prospectively enrolled in the Michigan Ford Influenza Vaccine Effectiveness (MFIVE) study, a subsite of the US Influenza Vaccine Effectiveness Network. All participants were tested by nasal-throat swab for RSV and influenza, including subtype, independently from clinician-directed testing. Participant illness characteristics and calculated multimorbidity-weighted index (MWI) were collected by in-person survey and electronic medical record review. Results Over 3 surveillance seasons (fall 2017 to spring 2020), 9.9% (n = 441) of 4442 participants had RSV detected. RSV-associated MAARI was more prevalent than influenza for participants 6 months to 4 years of age. Adults with RSV-MAARI had higher median MWI scores overall compared to influenza-MAARI and controls with neither virus (1.62, 0.40, and 0.64, respectively). Conclusions RSV is a significant, underrecognized cause of MAARI in both children and adults presenting for ambulatory care. Multimorbidity is an important contributor to RSV-associated MAARI in outpatient adults, providing information to support shared clinical decision making for vaccination. [ABSTRACT FROM AUTHOR]

Within a multistate clinical cohort, SARS-CoV-2 antiviral prescribing patterns were evaluated from April 2022–June 2023 among nonhospitalized patients with SARS-CoV-2 with risk factors for severe COVID-19. Among 3247 adults, only 31.9% were prescribed an antiviral agent (87.6% nirmatrelvir/ritonavir, 11.9% molnupiravir, 0.5% remdesivir), highlighting the need to identify and address treatment barriers. [ABSTRACT FROM AUTHOR]

Background There is evidence of an association of severe coroanavirus disease (COVID-19) outcomes with increased body mass index (BMI) and male sex. However, few studies have examined the interaction between sex and BMI on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral dynamics. Methods Participants conducted RT-PCR testing every 24–48 hours over a 15-day period. Sex and BMI were self-reported, and Ct values from E-gene were used to quantify viral load. Three distinct outcomes were examined using mixed-effects generalized linear models, linear models, and logistic models, respectively: all Ct values (model 1), nadir Ct value (model 2), and strongly detectable infection (at least 1 Ct value ≤28 during their infection) (model 3). An interaction term between BMI and sex was included, and inverse logit transformations were applied to quantify the differences by BMI and sex using marginal predictions. Results In total, 7988 participants enrolled in this study and 439 participants (model 1) and 309 (models 2 and 3) were eligible for these analyses. Among males, increasing BMI was associated with lower Ct values in a dose-response fashion. For participants with BMIs greater than 29 kg/m2, males had significantly lower Ct values and nadir Ct values than females. In total, 67.8% of males and 55.3% of females recorded a strongly detectable infection; increasing proportions of men had Ct values <28 with BMIs of 35 and 40 kg/m2. Conclusions We observed sex-based dimorphism in relation to BMI and COVID-19 viral load. Further investigation is needed to determine the cause, clinical impact, and transmission implications of this sex-differential effect of BMI on viral load. [ABSTRACT FROM AUTHOR]

Background Multiplex molecular diagnostic panels have greatly enhanced detection of gastrointestinal pathogens. However, data on the impact of these tests on clinical and patient-centered outcomes are limited. Methods We conducted a prospective, multicenter, stepped-wedge trial to determine the impact of multiplex molecular testing at 5 academic children's hospitals on children presenting to the emergency department with acute gastroenteritis. Caregivers were interviewed on enrollment and 7–10 days after enrollment to determine symptoms, risk factors, subsequent medical visits, and impact on family members. During the pre-intervention period, diagnostic testing was performed at the clinician's discretion. During the intervention period, multiplex molecular testing was performed on all children, with results available to clinicians. The primary outcome was return visits to a healthcare provider within 10 days of enrollment. Results Potential pathogens were identified by clinician-ordered tests in 19 of 571 (3.3%) in the pre-intervention period compared with 434 of 586 (74%) in the intervention period; clinically relevant pathogens were detected in 2.1% and 15%, respectively. In the multivariate model, the intervention was associated with a 21% reduction in the odds of any return visit (odds ratio, 0.79; 95% confidence interval,.70–.90) after adjusting for potential confounders. Appropriate treatment was prescribed in 11.3% compared with 19.6% during the intervention period (P =.22). Conclusions Routine molecular multiplex testing for all children who presented to the ED with acute gastroenteritis detected more clinically relevant pathogens and led to a 21% decrease in return visits. Additional research is needed to define patients most likely to benefit from testing. Clinical Trials Registration. NCT02248285. [ABSTRACT FROM AUTHOR]

Background Enterococcus intestinal domination (EID), a state of dysbiosis wherein enterococci comprise ≥30% abundance within the microbiota, has been associated with Enterococcus bacteremia, graft-versus-host disease, and mortality in the allogeneic hematopoietic stem cell transplant (allo HCT) population. The acute leukemia (AL) chemotherapy population includes patients receiving intensive chemotherapy, but not all patients go on to have an allo HCT. The impact of EID on outcomes including mortality in the AL chemotherapy population is unknown. Methods Microbiota composition from weekly stool samples was analyzed using 16S ribosomal RNA gene sequencing. Patients were analyzed in 2 cohorts: AL chemotherapy cohort and allo HCT cohort. α -diversity and richness were calculated. Kaplan-Meier analysis was used to analyze mortality. Results A total of 929 stool samples were collected from 139 patients. Both allo HCT and AL cohorts had a decline in α-diversity and richness over the course of treatment that tended not to return to baseline months later. EID was observed in at least 1 sample in 36% of allo HCT patients and 49% of AL patients. Patients with observed EID had lower α-diversity over time. Similar to the HCT cohort, AL patients with EID had reduced overall survival. We identified 4 other genera that were commonly found in ≥30% relative abundance within the microbiota, but none were associated with mortality. In fact, in allo HCT, Bacteroides abundance ≥30% was associated with improved survival. Conclusions EID is associated with increased all-cause mortality in HCT and AL cohorts. Unlike EID, relative abundance ≥30% by other genera is not associated with increased all-cause mortality. [ABSTRACT FROM AUTHOR]

In a 3-year period, 38 of 48 persons testing positive for hepatitis E virus (HEV) immunoglobulin M in Los Angeles County did not meet the acute HEV case definition. Healthcare providers should restrict HEV serologic testing for persons with clinically compatible symptoms or epidemiologic risk factors. [ABSTRACT FROM AUTHOR]

The article discusses research by Piero Olliaro and colleagues, reported in the Clinical Infectious Diseases journal in 2023. It mentions that the research focuses on three randomized trials conducted in Burkina Faso, Ghana, and Uganda. It mentions that the research focuses on three randomized trials conducted in Burkina Faso, Ghana, and Uganda.

Background Acute myocardial infarction (AMI) events have been reported among patients with certain viral and bacterial infections. Whether invasive pneumococcal disease (IPD) increases the risk of AMI remains unclear. We examined whether laboratory-confirmed IPD was associated with the risk of AMI. Methods We conducted a self-controlled case series analysis among adult Tennessee residents with evidence of an AMI hospitalization (2003–2019). Patient follow-up started 1 year before the earliest AMI and continued through the date of death, 1 year after AMI, or study end (December 2019). Periods for AMI assessment included the 7 to 1 days before IPD specimen collection (pre-IPD detection), day 0 through day 7 after IPD specimen collection (current IPD), day 8 to 28 after IPD specimen collection (post-IPD), and a control period (all other follow-up). We used conditional Poisson regression to calculate incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for each risk period compared with control periods using within-person comparisons. Results We studied 324 patients hospitalized for AMI with laboratory-confirmed IPD within 1 year before or after the AMI hospitalization. The incidence of AMI was significantly higher during the pre-IPD detection (IRR, 10.29; 95% CI: 6.33–16.73) and the current IPD (IRR, 92.95; 95% CI: 72.17–119.71) periods but nonsignificantly elevated in the post-IPD risk period (IRR, 1.83; 95% CI:.86–3.91) compared with control periods. The AMI incidence was higher in the post-IPD control period (29 to 365 days after IPD; IRR, 2.95; 95% CI: 2.01–4.32). Conclusions Hospitalizations with AMI were strongly associated with laboratory-confirmed IPD. [ABSTRACT FROM AUTHOR]

Background Current understanding of severe respiratory syncytial virus (RSV) infections in adults is limited by clinical underrecognition. We compared the prevalence, clinical characteristics, and outcomes of RSV infections vs influenza in adults hospitalized with acute respiratory illnesses (ARIs) in a prospective national surveillance network. Methods Hospitalized adults who met a standardized ARI case definition were prospectively enrolled across 3 respiratory seasons from hospitals participating across all sites of the US Hospitalized Adult Influenza Vaccine Effectiveness Network (2016–2019). All participants were tested for RSV and influenza using real-time reverse-transcription polymerase chain reaction assay. Multivariable logistic regression was used to test associations between laboratory-confirmed infection and characteristics and clinical outcomes. Results Among 10 311 hospitalized adults, 6% tested positive for RSV (n = 622), 18.8% for influenza (n = 1940), and 75.1% negative for RSV and influenza (n = 7749). Congestive heart failure (CHF) or chronic obstructive pulmonary disease (COPD) was more frequent with RSV than influenza (CHF: 37.3% vs 28.8%, P <.0001; COPD: 47.6% vs 35.8%, P <.0001). Patients with RSV more frequently had longer admissions (odds ratio [OR], 1.38; 95% confidence interval [CI], 1.06–1.80) for stays >1 week) and mechanical ventilation (OR, 1.45; 95% CI, 1.09–1.93) compared with influenza but not compared with the influenza-negative group (OR, 1.03; 95% CI,.82–1.28 and OR, 1.17; 95% CI,.91–1.49, respectively). Conclusions The prevalence of RSV across 3 seasons was considerable. Our findings suggest that those with RSV have worse outcomes compared with influenza and frequently have cardiopulmonary conditions. This study informs future vaccination strategies and underscores a need for RSV surveillance among adults with severe ARI. [ABSTRACT FROM AUTHOR]

Background In the United States, influenza activity during the 2021–2022 season was modest and sufficient enough to estimate influenza vaccine effectiveness (VE) for the first time since the beginning of the coronavirus disease 2019 pandemic. We estimated influenza VE against laboratory-confirmed outpatient acute illness caused by predominant A(H3N2) viruses. Methods Between October 2021 and April 2022, research staff across 7 sites enrolled patients aged ≥6 months seeking outpatient care for acute respiratory illness with cough. Using a test-negative design, we assessed VE against influenza A(H3N2). Due to strong correlation between influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, participants who tested positive for SARS-CoV-2 were excluded from VE estimations. Estimates were adjusted for site, age, month of illness, race/ethnicity, and general health status. Results Among 6260 participants, 468 (7%) tested positive for influenza only, including 440 (94%) for A(H3N2). All 206 sequenced A(H3N2) viruses were characterized as belonging to genetic group 3C.2a1b subclade 2a.2, which has antigenic differences from the 2021–2022 season A(H3N2) vaccine component that belongs to clade 3C.2a1b subclade 2a.1. After excluding 1948 SARS-CoV-2–positive patients, 4312 patients were included in analyses of influenza VE; 2463 (57%) were vaccinated against influenza. Effectiveness against A(H3N2) for all ages was 36% (95% confidence interval, 20%–49%) overall. Conclusions Influenza vaccination in 2021–2022 provided protection against influenza A(H3N2)-related outpatient visits among young persons. [ABSTRACT FROM AUTHOR]

The article discusses the specialization of Aedes aegypti mosquitoes in feeding on humans as opposed to other vertebrate animals. It explores how changes in climate, urbanization, and historical events like the African slave trade have influenced the mosquito's preference for humans, increasing the risk of diseases like yellow fever, dengue, chikungunya, and Zika virus in urban areas of Africa and beyond.

Background Acute respiratory infections (ARI) are the most common infectious diseases globally. Community surveillance may provide a more comprehensive picture of disease burden than medically attended illness alone. Methods In this longitudinal study conducted from 2012 to 2017 in the Washington Heights/Inwood area of New York City, we enrolled 405 households with 1915 individuals. Households were sent research text messages twice weekly inquiring about ARI symptoms. Research staff confirmed symptoms by follow-up call. If ≥2 criteria for ARI were met (fever/feverish, cough, congestion, pharyngitis, myalgias), staff obtained a mid-turbinate nasal swab in participants' homes. Swabs were tested using the FilmArray reverse transcription polymerase chain reaction (RT-PCR) respiratory panel. Results Among participants, 43.9% were children, and 12.8% had a chronic respiratory condition. During the 5 years, 114 724 text messages were sent; the average response rate was 78.8% ± 6.8%. Swabs were collected for 91.4% (2756/3016) of confirmed ARI; 58.7% had a pathogen detected. Rhino/enteroviruses (51.9%), human coronaviruses (13.9%), and influenza (13.2%) were most commonly detected. The overall incidence was 0.62 ARI/person-year, highest (1.73) in <2 year-olds and lowest (0.46) in 18–49 year-olds. Approximately one-fourth of those with ARI sought healthcare; percents differed by pathogen, demographic factors, and presence of a chronic respiratory condition. Conclusions Text messaging is a novel method for community-based surveillance that could be used both seasonally as well as during outbreaks, epidemics and pandemics. The importance of community surveillance to accurately estimate disease burden is underscored by the findings of low rates of care-seeking that varied by demographic factors and pathogens. [ABSTRACT FROM AUTHOR]

Background Sepsis causes a major health burden in the United States. To better understand the role of sepsis as a driver of the burden and cost of foodborne illness in the United States, we estimated the frequency and treatment cost of sepsis among US patients hospitalized with 31 pathogens commonly transmitted through food or with unspecified acute gastrointestinal illness (AGI). Methods Using data from the National Inpatient Sample from 2012 to 2015, we identified sepsis hospitalizations using 2 approaches—explicit ICD-9-CM codes for sepsis and a coding scheme developed by Angus that identifies sepsis using specific ICD-9-CM diagnosis codes indicating an infection plus organ failure. We examined differences in the frequency and the per-case cost of sepsis across pathogens and AGI and estimated total hospitalization costs using prior estimates of foodborne hospitalizations. Results Using Explicit Sepsis Codes, sepsis hospitalizations accounted for 4.6% of hospitalizations with a pathogen commonly transmitted through food or unspecified AGI listed as a diagnosis; this was 33.2% using Angus Sepsis Codes. The average per-case cost was $35 891 and $20 018, respectively. Applying the proportions of hospitalizations with sepsis from this study to prior estimates of the number foodborne hospitalizations, the total annual cost was $248 million annually using Explicit Sepsis Codes and $889 million using Angus Sepsis Codes. Conclusions Sepsis is a serious complication among patients hospitalized with a foodborne pathogen infection or AGI resulting in a large burden of illness. Hospitalizations that are diagnosed using explicit sepsis codes are more severe and costly, but likely underestimate the burden of foodborne sepsis. [ABSTRACT FROM AUTHOR]

Background Most children recover quickly after coronavirus disease 2019 (COVID-19), but some may have ongoing symptoms. Follow-up studies have been limited by small sample sizes and lack of appropriate controls. Methods We used national testing data to identify children aged 2–16 years with a SARS-CoV-2 PCR test during 1–7 January 2021 and randomly selected 1500 PCR-positive cases and 1500 matched PCR-negative controls. Parents were asked to complete a questionnaire about the acute illness and prespecified neurological, dermatological, sensory, respiratory, cardiovascular, gastrointestinal, mental health (including emotional and behavioral well-being), and other symptoms experienced ≥5 times at 1 month after the PCR test. Results Overall, 35.0% (859/2456) completed the questionnaire, including 38.0% (472/1242) of cases and 32% (387/1214) of controls, of whom 68% (320/472) and 40% (154/387) were symptomatic, respectively. The most prevalent acute symptoms were cough (249/859, 29.0%), fever (236/859, 27.5%), headache (236/859, 27.4%), and fatigue (231/859, 26.9%). One month later, 21/320 (6.7%) of symptomatic cases and 6/154 (4.2%) of symptomatic controls (P  = .24) experienced ongoing symptoms. Of the 65 ongoing symptoms solicited, 3 clusters were significantly (P  < .05) more common, albeit at low prevalence, among symptomatic cases (3–7%) than symptomatic controls (0–3%): neurological, sensory, and emotional and behavioral well-being. Mental health symptoms were reported by all groups but more frequently among symptomatic cases than symptomatic controls or asymptomatic children. Conclusions Children with symptomatic COVID-19 had a slightly higher prevalence of ongoing symptoms than symptomatic controls, and not as high as previously reported. Healthcare resources should be prioritized to support the mental health of children. [ABSTRACT FROM AUTHOR]

Background To combat the coronavirus disease 2019 (COVID-19) pandemic, nonpharmaceutical interventions (NPIs) were implemented worldwide, which impacted a broad spectrum of acute respiratory infections (ARIs). Methods Etiologically diagnostic data from 142 559 cases with ARIs, who were tested for 8 viral pathogens (influenza virus [IFV], respiratory syncytial virus [RSV], human parainfluenza virus [HPIV], human adenovirus [HAdV], human metapneumovirus [HMPV], human coronavirus [HCoV], human bocavirus [HBoV], and human rhinovirus [HRV]) between 2012 and 2021, were analyzed to assess the changes in respiratory infections in China during the first COVID-19 pandemic year compared with pre-pandemic years. Results Test-positive rates of all respiratory viruses decreased during 2020, compared to the average levels during 2012–2019, with changes ranging from −17.2% for RSV to −87.6% for IFV. Sharp decreases mostly occurred between February and August when massive NPIs remained active, although HRV rebounded to the historical level during the summer. While IFV and HMPV were consistently suppressed year-round, RSV, HPIV, HCoV, HRV, and HBoV resurged and went beyond historical levels during September 2020–January 2021, after NPIs were largely relaxed and schools reopened. Resurgence was more prominent among children <18 years and in northern China. These observations remain valid after accounting for seasonality and long-term trend of each virus. Conclusions Activities of respiratory viral infections were reduced substantially in the early phases of the COVID-19 pandemic, and massive NPIs were likely the main driver. Lifting of NPIs can lead to resurgence of viral infections, particularly in children. [ABSTRACT FROM AUTHOR]

Background It is unknown if probiotics exert pathogen-specific effects in children with diarrhea secondary to acute gastroenteritis. Methods Analysis of patient-level data from 2 multicenter randomized, placebo controlled trials conducted in pediatric emergency departments in Canada and the United States. Participants were 3–48 months with > 3 diarrheal episodes in the preceding 24 hours and were symptomatic for <72 hours and <7 days in the Canadian and US studies, respectively. Participants received either placebo or a probiotic preparation (Canada- Lactobacillus rhamnosus R0011/ Lactobacillus helveticus R0052; US- L. rhamnosus GG). The primary outcome was post-intervention moderate-to-severe disease (ie, ≥9 on the Modified Vesikari Scale [MVS] score). Results Pathogens were identified in specimens from 59.3% of children (928/1565). No pathogen groups were less likely to experience an MVS score ≥9 based on treatment allocation (test for interaction = 0.35). No differences between groups were identified for adenovirus (adjusted relative risk [aRR]: 1.42; 95% confidence interval [CI]:.62, 3.23), norovirus (aRR: 0.98; 95% CI:.56, 1.74), rotavirus (aRR: 0.86; 95% CI:.43, 1.71) or bacteria (aRR: 1.19; 95% CI:.41, 3.43). At pathogen-group and among individual pathogens there were no differences in diarrhea duration or the total number of diarrheal stools between treatment groups, regardless of intervention allocation or among probiotic sub-groups. Among adenovirus-infected children, those administered the L. rhamnosus R0011/ L. helveticus R0052 product experienced fewer diarrheal episodes (aRR: 0.65; 95% CI:.47,.90). Conclusions Neither probiotic product resulted in less severe disease compared to placebo across a range of the most common etiologic pathogens. The preponderance of evidence does not support the notion that there are pathogen specific benefits associated with probiotic use in children with acute gastroenteritis. Clinical Trials Registration NCT01773967 and NCT01853124. [ABSTRACT FROM AUTHOR]

Background Antibiotics are considered to be among the most frequent causes of drug-related acute liver injury (ALI). Although many ALIs have mild and reversible clinical outcomes, there is substantial risk of severe reactions leading to acute liver failure, need for liver transplant, and death. Recent studies have raised concerns of hepatotoxic potential related to the use of fluoroquinolones. Methods This study examined the risk of ALI associated with oral fluoroquinolone treatment compared with amoxicillin (419 930 courses, propensity score matched 1:1). The information on drug use was collected from a national, registry-based cohort derived from all Swedish adults aged 40–85 years. Results During a follow-up period of 60 days, users of oral fluoroquinolones had a >2-fold risk of ALI compared to users of amoxicillin (hazard ratio, 2.32 [95% confidence interval {CI}, 1.01–5.35). The adjusted absolute risk difference for use of fluoroquinolones as compared to amoxicillin was 4.94 (95% CI,.04–16.3) per 1 million episodes. Conclusions In this propensity score–matched study, fluoroquinolone treatment was associated with an increased risk of ALI in the first 2 months after starting treatment. [ABSTRACT FROM AUTHOR]

Background Intestinal disorders such as environmental enteric dysfunction (EED) are prevalent in low- and middle-income countries (LMICs) and important contributors to childhood undernutrition and mortality. Autopsies are rarely performed in LMICs but minimally invasive tissue sampling is increasingly deployed as a more feasible and acceptable procedure, although protocols have been devoid of intestinal sampling to date. We sought to determine (1) the feasibility of postmortem intestinal sampling, (2) whether autolysis precludes enteric biopsies' utility, and (3) histopathologic features among children who died during hospitalization with acute illness or undernutrition. Methods Transabdominal needle and endoscopic forceps upper and lower intestinal sampling were conducted among children aged 1 week to 59 months who died while hospitalized in Blantyre, Malawi. Autolysis ratings were determined for each hematoxylin and eosin slide, and upper and lower intestinal scoring systems were adapted to assess histopathologic features and their severity. Results Endoscopic and transabdominal sampling procedures were attempted in 28 and 14 cases, respectively, with >90% success obtaining targeted tissue. Varying degrees of autolysis were present in all samples and precluded histopathologic scoring of 6% of 122 biopsies. Greater autolysis in duodenal samples was seen with longer postmortem interval (Beta = 0.06, 95% confidence interval, 0.02–0.11). Histopathologic features identified included duodenal Paneth and goblet cell depletion. Acute inflammation was absent but chronic inflammation was prevalent in both upper and lower enteric samples. Severe chronic rectal inflammation was identified in children as young as 5.5 weeks. Conclusions Minimally invasive postmortem intestinal sampling is feasible and identifies histopathology that can inform mortality contributors. [ABSTRACT FROM AUTHOR]

Background Rotavirus is the leading cause of acute gastroenteritis (AGE) among children worldwide. Prior to rotavirus vaccine introduction, over one third of AGE hospitalizations in Africa were due to rotavirus. We describe the impact of rotavirus vaccines using data from the African Rotavirus Surveillance Network (ARSN). Methods For descriptive analysis, we included all sites reporting to ARSN for any length of time between 2008 and 2018. For vaccine impact analysis, continuous surveillance throughout the year was required to minimize potential bias due to enrollment of partial seasons and sites had to report a minimum of 100 AGE cases per year. We report the proportion of rotavirus AGE cases by year relative to vaccine introduction, and the relative reduction in the proportion of rotavirus AGE cases reported following vaccine introduction. Results From 2008 to 2018, 97 366 prospectively enrolled hospitalized children <5 years of age met the case definition for AGE, and 34.1% tested positive for rotavirus. Among countries that had introduced rotavirus vaccine, the proportion of hospitalized AGE cases positive for rotavirus declined from 39.2% in the prevaccine period to 25.3% in the postvaccine period, a 35.5% (95% confidence interval [CI]: 33.7–37.3) decline. No declines were observed among countries that had not introduced the vaccine over the 11-year period. Conclusions Rotavirus vaccine introduction led to large and consistent declines in the proportion of hospitalized AGE cases that are positive for rotavirus. To maximize the public health benefit of these vaccines, efforts to introduce rotavirus vaccines in the remaining countries in the region and to improve coverage should continue. [ABSTRACT FROM AUTHOR]

Background The etiology and optimal clinical management of acute febrile illness (AFI) is poorly understood. Methods Blood samples taken from study participants with acute fever (≥37.5°C) or a history of fever and recruited into the previous Typhoid Fever Surveillance in Africa (TSAP) study were evaluated using a polymerase chain reaction (PCR)-based TaqMan-Array Card designed to detect a panel of bacterial, viral, and parasitic pathogens. Clinical metadata were also assessed. Results A total of 615 blood samples available for analysis originated from Burkina Faso (n = 53), Madagascar (n = 364), and Sudan (n = 198) and were taken from participants ranging in age from 0–19 years. Through the TaqMan-Array Card, at least 1 pathogen was detected in 62% (33 of 53), 24% (86 of 364), and 60% (118 of 198) of specimens from Burkina Faso, Madagascar, and Sudan, respectively. The leading identified pathogen overall was Plasmodium spp. accounting for 47% (25 of 53), 2.2% (8 of 364), and 45% (90 of 198) of AFI at the respective sites. In Madagascar, dengue virus was the most prevalent pathogen (10.2%). Overall, 69% (357 of 516) of patients with clinical diagnoses of malaria, respiratory infection, or gastrointestinal infection were prescribed a World Health Organization guideline-recommended empiric antibiotic, whereas only 45% (106 of 237) of patients with pathogens detected were treated with an antibiotic exerting likely activity. Conclusions A PCR approach for identifying multiple bacterial, viral, and parasitic pathogens in whole blood unveiled a diversity of previously undetected pathogens in AFI cases and carries implications for the appropriate management of this common syndrome. [ABSTRACT FROM AUTHOR]

The risk of reactivation of resolved hepatitis B virus (HBV) in hepatitis B surface antigen (HBsAg)-negative multiple myeloma patients after daratumumab has not been reported. Among 93 patients with daratumumab treatment, reactivation occurred in 6 patients (6.5%) with one hepatic failure. This is the first report demonstrating a considerable risk of reactivation of resolved HBV after daratumumab. [ABSTRACT FROM AUTHOR]

Background Although multiple respiratory viruses circulate in humans, few studies have compared the incidence of different viruses across the life course. We estimated the incidence of outpatient illness due to 12 different viruses during November 2018 through April 2019 in a fully enumerated population. Methods We conducted active surveillance for ambulatory care visits for acute respiratory illness (ARI) among members of Kaiser Permanente Washington (KPWA). Enrolled patients provided respiratory swab specimens which were tested for 12 respiratory viruses using reverse transcription polymerase chain reaction (RT-PCR). We estimated the cumulative incidence of infection due to each virus overall and by age group. Results The KPWA population under surveillance included 202 562 individuals, of whom 2767 (1.4%) were enrolled in the study. Influenza A(H3N2) was the most commonly detected virus, with an overall incidence of 21 medically attended illnesses per 1000 population; the next most common viruses were influenza A(H1N1) (18 per 1000), coronaviruses (13 per 1000), respiratory syncytial virus (RSV, 13 per 1000), and rhinovirus (9 per 1000). RSV was the most common cause of medically attended ARI among children aged 1–4 years; coronaviruses were the most common among adults aged ≥65 years. Conclusions Consistent with other studies focused on single viruses, we found that influenza and RSV were major causes of acute respiratory illness in persons of all ages. In comparison, coronaviruses and rhinovirus were also important pathogens. Prior to the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coronaviruses were the second-most common cause of medically attended ARI during the 2018/19 influenza season. [ABSTRACT FROM AUTHOR]

Background The Core Elements of Outpatient Antibiotic Stewardship provide a framework to improve antibiotic use. We report the impact of core elements implementation within Veterans Health Administration sites. Methods In this quasiexperimental controlled study, effects of an intervention targeting antibiotic prescription for uncomplicated acute respiratory tract infections (ARIs) were assessed. Outcomes included per-visit antibiotic prescribing, treatment appropriateness, ARI revisits, hospitalization, and ARI diagnostic changes over a 3-year pre-implementation period and 1-year post-implementation period. Logistic regression adjusted for covariates (odds ratio [OR], 95% confidence interval [CI]) and a difference-in-differences analysis compared outcomes between intervention and control sites. Results From 2014–2019, there were 16 712 and 51 275 patient visits within 10 intervention and 40 control sites, respectively. Antibiotic prescribing rates pre- and post-implementation within intervention sites were 59.7% and 41.5%, compared to 73.5% and 67.2% within control sites, respectively (difference-in-differences, P <.001). Intervention site pre- and post-implementation OR to receive appropriate therapy increased (OR, 1.67; 95% CI, 1.31–2.14), which remained unchanged within control sites (OR,1.04; 95% CI,.91–1.19). ARI-related return visits post-implementation (–1.3% vs –2.0%; difference-in-differences P =.76) were not different, but all-cause hospitalization was lower within intervention sites (–0.5% vs –0.2%; difference-in-differences P =.02). The OR to diagnose non-specific ARI compared with non-ARI diagnoses increased post-implementation forintervention (OR, 1.27; 95% CI, 1.21 –1.34) but not control (OR, 0.97; 95% CI,.94–1.01) sites. Conclusions Implementation of the core elements was associated with reduced antibiotic prescribing for RIs and a reduction in hospitalizations. Diagnostic coding changes were observed. [ABSTRACT FROM AUTHOR]

Background Long-term health sequelae of coronavirus disease 2019 (COVID-19) may be multiple but have thus far not been systematically studied. Methods All patients discharged after COVID-19 from the Radboud University Medical Center, Nijmegen, the Netherlands, were consecutively invited to a multidisciplinary outpatient facility. Also, nonadmitted patients with mild disease but with symptoms persisting >6 weeks could be referred by general practitioners. Patients underwent a standardized assessment including measurements of lung function, chest computed tomography (CT)/X-ray, 6-minute walking test, body composition, and questionnaires on mental, cognitive, health status, and quality of life (QoL). Results 124 patients (59 ± 14 years, 60% male) were included: 27 with mild, 51 with moderate, 26 with severe, and 20 with critical disease. Lung diffusion capacity was below the lower limit of normal in 42% of discharged patients. 99% of discharged patients had reduced ground-glass opacification on repeat CT imaging, and normal chest X-rays were found in 93% of patients with mild disease. Residual pulmonary parenchymal abnormalities were present in 91% of discharged patients and correlated with reduced lung diffusion capacity. Twenty-two percent had low exercise capacity, 19% low fat-free mass index, and problems in mental and/or cognitive function were found in 36% of patients. Health status was generally poor, particularly in the domains functional impairment (64%), fatigue (69%), and QoL (72%). Conclusions This comprehensive health assessment revealed severe problems in several health domains in a substantial number of ex–COVID-19 patients. Longer follow-up studies are warranted to elucidate natural trajectories and to find predictors of complicated long-term trajectories of recovery. [ABSTRACT FROM AUTHOR]

Background Acute gastroenteritis (AGE) causes a substantial burden in the United States, but its etiology frequently remains undetermined. Active surveillance within an integrated healthcare delivery system was used to estimate the prevalence and incidence of medically attended norovirus, rotavirus, sapovirus, and astrovirus. Methods Active surveillance was conducted among all enrolled members of Kaiser Permanente Northwest during July 2014–June 2016. An age-stratified, representative sample of AGE-associated medical encounters were recruited to provide a stool specimen to be tested for norovirus, rotavirus, sapovirus, and astrovirus. Medically attended AGE (MAAGE) encounters for a patient occurring within 30 days were grouped into 1 episode, and all-cause MAAGE incidence was calculated. Pathogen- and healthcare setting–specific incidence estimates were calculated using age-stratified bootstrapping. Results The overall incidence of MAAGE was 40.6 episodes per 1000 person-years (PY), with most episodes requiring no more than outpatient care. Norovirus was the most frequently detected pathogen, with an incidence of 5.5 medically attended episodes per 1000 PY. Incidence of norovirus MAAGE was highest among children aged < 5 years (20.4 episodes per 1000 PY), followed by adults aged ≥ 65 years (4.5 episodes per 1000 PY). Other study pathogens showed similar patterns by age, but lower overall incidence (sapovirus: 2.4 per 1000 PY; astrovirus: 1.3 per 1000 PY; rotavirus: 0.5 per 1000 PY). Conclusions Viral enteropathogens, particularly norovirus, are important contributors to MAAGE, especially among children < 5 years of age. The present findings underline the importance of judicious antibiotics use for pediatric AGE and suggest that an effective norovirus vaccine could substantially reduce MAAGE. [ABSTRACT FROM AUTHOR]

Background Acute encephalitis/encephalopathy (AE) associated with viral and other pathogens leads to neurological sequelae and mortality. Knowing the prognostic factors is therefore important for immediate interventions. We examined early-phase unfavorable prognostic factors among children with AE using a nationwide database. Methods We performed a retrospective cohort study using the Diagnosis Procedure Combination database, which includes approximately half of acute-care inpatients across Japan. We enrolled children aged ≤ 18 years who were hospitalized for AE and discharged from April 2010 to March 2018. The composite unfavorable outcome included the following at discharge: in-hospital death, tracheostomy, enteral tube feeding, and physical rehabilitation. Unfavorable prognostic factors were assessed using a multivariable Poisson regression model including patient characteristics, associated pathogens, and interventions within 2 days of admission adjusting for within-hospital clustering. Results This study included 9386 children with AE (median age, 3 years). A total of 241 (2.6%) in-hospital deaths occurred, and 2027 (21.6%) patients had the composite unfavorable outcome. Significant unfavorable prognostic factors were age 12–18 years, congenital anomalies, epilepsy, and Japan Coma Scale score of 100–300 at admission (ie, worse levels of consciousness). In contrast, herpes simplex virus infection and influenza virus infection were associated with favorable outcomes. Conclusions We identified early-phase (within 2 days of admission) unfavorable prognostic factors among children with AE. These findings will help identify patients who may benefit from early aggressive therapeutic interventions. [ABSTRACT FROM AUTHOR]

Background Group A Streptococcus (GAS) is a leading cause of acute respiratory conditions that frequently result in antibiotic prescribing. Vaccines against GAS are currently in development. Methods We estimated the incidence rates of healthcare visits and antibiotic prescribing for pharyngitis, sinusitis, and acute otitis media (AOM) in the United States using nationally representative surveys of outpatient care provision, supplemented by insurance claims data. We estimated the proportion of these episodes attributable to GAS and to GAS emm types included in a proposed 30-valent vaccine. We used these outputs to estimate the incidence rates of outpatient visits and antibiotic prescribing preventable by GAS vaccines with various efficacy profiles under infant and school-age dosing schedules. Results GAS pharyngitis causes 19.1 (95% confidence interval [CI], 17.3–21.1) outpatient visits and 10.2 (95% CI, 9.0–11.5) antibiotic prescriptions per 1000 US persons aged 0–64 years, annually. GAS pharyngitis causes 93.2 (95% CI, 82.3–105.3) visits and 53.2 (95% CI, 45.2–62.5) antibiotic prescriptions per 1000 children ages 3–9 years, annually, representing 5.9% (95% CI, 5.1–7.0%) of all outpatient antibiotic prescribing in this age group. Collectively, GAS-attributable pharyngitis, sinusitis, and AOM cause 26.9 (95% CI, 23.9–30.8) outpatient visits and 16.1 (95% CI, 14.0–18.7) antibiotic prescriptions per 1000 population, annually. A 30-valent GAS vaccine meeting the World Health Organization's 80% efficacy target could prevent 5.4% (95% CI, 4.6–6.4%) of outpatient antibiotic prescriptions among children aged 3–9 years. If vaccine prevention of GAS pharyngitis made the routine antibiotic treatment of pharyngitis unnecessary, up to 17.1% (95% CI, 15.0–19.6%) of outpatient antibiotic prescriptions among children aged 3–9 years could be prevented. Conclusions An efficacious GAS vaccine could prevent substantial incidences of pharyngitis infections and associated antibiotic prescribing in the United States. [ABSTRACT FROM AUTHOR]

HIV transmission is increased during acute and early HIV (AEH). Rapid antiretroviral therapy may shorten the duration of infectivity. We show rapid antiretroviral therapy in AEH is acceptable and effective, with 69.0% of participants starting ART within 7 days of HIV diagnosis disclosure, and 88.1% achieving suppression by 48 weeks. [ABSTRACT FROM AUTHOR]

We report two fatal cases of acute liver failure secondary to herpes simplex virus 1 infection in COVID-19 patients, following tocilizumab and corticosteroid therapy. Screening for and prompt recognition of herpes simplex virus 1 reactivation in these patients, undergoing immunomodulatory treatment, may have potentially relevant clinical consequences. [ABSTRACT FROM AUTHOR]

Background Interventions to tackle the coronavirus disease 2019 (COVID-19) pandemic may affect the burden of other respiratory diseases. Considering the repercussions of these unique social experiences to infant health, this study aims to assess the early impact of social distancing due to the COVID-19 pandemic in hospital admissions for acute bronchiolitis. Methods Data from hospitalizations of acute bronchiolitis in infants <1 year of age were obtained from the Department of Informatics of the Brazilian Public Health database for the period between 2016 and 2020. These data were also analyzed by macroregions of Brazil (North, Northeast, Southeast, South, and Midwest). To evaluate the effect of social distancing strategy on the incidence of acute bronchiolitis, the absolute and relative reductions were calculated by analyzing the yearly subsets of 2016 vs 2020, 2017 vs 2020, 2018 vs 2020, and 2019 vs 2020. Results There was a significant reduction in all comparisons, ranging from −78% (incidence rate ratio [IRR], 0.22 [95% confidence interval {CI},.20–.24]) in 2016 vs 2020 to −85% (IRR, 0.15 [95% CI,.13–.16]) in 2019 vs 2020, for the data from Brazil. For analyses by macroregions, the reduction varied from −58% (IRR, 0.41 [95% CI,.37–.45]) in the Midwest in 2016 vs 2020 to −93% (IRR, 0.07 [95% CI,.06–.08]) in the South in 2019 vs 2020. Conclusions There was a significant reduction in hospitalization for acute bronchiolitis in children <1 year old in Brazil, on the order of >70% for most analysis. Our data suggest an important impact of social distancing on reducing the transmission of viruses related to acute bronchiolitis. Such knowledge may guide strategies for prevention of viral spread. [ABSTRACT FROM AUTHOR]

Background Rotavirus is a common cause of severe pediatric acute gastroenteritis. Two vaccines are licensed in the United States and have demonstrated high effectiveness against moderate to severe disease. However, fewer data are available on rotavirus vaccine effectiveness (VE) against milder disease. Methods We leveraged active surveillance data from Kaiser Permanente Northwest to calculate rotavirus VE against medically attended rotavirus illness among age-eligible children. We utilized a test-negative case-control design and applied 4 distinct case definitions based on reverse transcription–quantitative real-time PCR (qRT-PCR) assay and enzyme immunoassay (EIA) test results. VE was calculated as 100 × (1 − odds ratio), and models were adjusted for age group. Results The VE analysis population comprised 842 children, 799 (95%) of whom had mild disease requiring at most a clinic visit and 698 (83%) of whom were fully vaccinated against rotavirus. Age-adjusted VE was 70% (95% confidence interval [CI], 37–86%) against disease defined solely by qRT-PCR results, 72% (95% CI, 31–89%) against disease as defined by qRT-PCR with a quantification cycle (C q ) value <27, 73% (95% CI, 32–90%) against disease that was qRT-PCR positive but EIA negative, and 62% (95% CI, –20–88%) against disease defined solely by EIA. Results were similar when restricting to disease resulting in at most an ambulatory clinic or emergency department visit. Conclusions These results support the effectiveness of rotavirus vaccination in protecting US children from mild to moderate and severe disease. Our findings are also useful to show the effectiveness of rotavirus vaccination against qRT-PCR–defined illness. [ABSTRACT FROM AUTHOR]

Background Diagnosis of schistosomiasis remains elusive soon after infection. We evaluated several diagnostic methods in a cluster of travelers with simultaneous freshwater exposure in South Africa. Methods Eosinophil count, schistosome antibody tests, stool and urine microscopy, and serum Dra1 PCR assays were performed at weeks 4–5 (early symptomatic phase), 7–8 (praziquantel treatment), and 13–14 (after treatment). Sequencing was done on serum samples from 3 patients to identify the species. Results Of the 34 travelers (16 adults and 18 children), 32 developed symptoms 2–6 weeks after exposure. A raised eosinophil count (>750/µL) was seen in 12 of 33 at weeks 4–5, and in 22 of 34 at weeks 7–8. Schistosoma antibodies were detected in 3 of 33 at weeks 4–5 and in 12 of 34 at weeks 7–8 and weeks 13–14. The Dra1 PCR result was positive in 24 of 33 travelers at weeks 4–5, in 31 of 34 at weeks 7–8, in 25 of 34 at weeks 13–14, and at least once in all. Ova were absent in all urine and stool samples obtained. Sequencing identified Schistosoma mattheei nuclear and Schistosoma haematobium mitochondrial DNA, indicative of a hybrid species. Conclusions The Dra1 PCR confirmed the diagnosis in all exposed travelers at a much earlier stage than conventional tests. The causative species is probably an S. mattheei × S. haematobium hybrid. [ABSTRACT FROM AUTHOR]

Our objective was to describe the duration of antibiotic therapy for the management of common outpatient conditions. The median duration of antibiotic courses for most common conditions, except for acute cystitis, was 10 days, in many cases exceeding guideline-recommended durations. [ABSTRACT FROM AUTHOR]

Orally-transmitted acute Chagas disease (CD) is emerging as an important public health problem. The prognosis of acute infection following oral transmission is unknown. The aim of this study was to analyze and summarize data on orally-transmitted acute CD. We searched for publications from 1968 to 31 January 2018. We included studies and unpublished data from government sources that reported patients with acute orally-transmitted CD. We identified 41 papers and we added 932 unpublished cases. In all, our study covered 2470 cases and occurrence of 97 deaths. Our meta-analysis estimated that the case-fatality rate was 1.0% (95% CI 0.0–4.0%). Lethality rates have declined over time (P  = .02). In conclusion, orally-transmitted acute CD has considerable lethality in the first year after infection. The lethality in symptomatic cases is similar to that from other routes of infection. The lethality rate of orally-acquired disease has declined over the years. [ABSTRACT FROM AUTHOR]

Background Patients with coronavirus disease 2019 (COVID-19) experience a wide clinical spectrum, with over 2% developing fatal outcome. The prognostic factors for fatal outcome remain sparsely investigated. Methods A retrospective cohort study was performed in a cohort of patients with confirmed COVID-19 in one designated hospital in Wuhan, China, from 17 January–5 March 2020. The laboratory parameters and a panel of cytokines were consecutively evaluated until patients' discharge or death. The laboratory features that could be used to predict fatal outcome were identified. Results Consecutively collected data on 55 laboratory parameters and cytokines from 642 patients with COVID-19 were profiled along the entire disease course, based on which 3 clinical stages (acute stage, days 1–9; critical stage, days 10–15; and convalescence stage, day 15 to observation end) were determined. Laboratory findings based on 75 deceased and 357 discharged patients revealed that, at the acute stage, fatality could be predicted by older age and abnormal lactate dehydrogenase (LDH), urea, lymphocyte count, and procalcitonin (PCT) level. At the critical stage, the fatal outcome could be predicted by age and abnormal PCT, LDH, cholinesterase, lymphocyte count, and monocyte percentage. Interleukin 6 (IL-6) was remarkably elevated, with fatal cases having a more robust production than discharged cases across the whole observation period. LDH, PCT, lymphocytes, and IL-6 were considered highly important prognostic factors for COVID-19–related death. Conclusions The identification of predictors that were routinely tested might allow early identification of patients at high risk of death for early aggressive intervention. [ABSTRACT FROM AUTHOR]

Background Acute gastroenteritis (AGE) is a common reason for children to receive medical care. However, the viral etiology of AGE illness is not well described in the post–rotavirus vaccine era, particularly in the outpatient (OP) setting. Methods Between 2012 and 2015, children 15 days through 17 years old presenting to Vanderbilt Children's Hospital, Nashville, Tennessee, with AGE were enrolled prospectively from the inpatient, emergency department, and OP settings, and stool specimens were collected. Healthy controls (HCs) were enrolled and frequency matched for period, age group, race, and ethnicity. Stool specimens were tested by means of reverse-transcription real-time quantitative polymerase chain reaction for norovirus, sapovirus, and astrovirus RNA and by Rotaclone enzyme immunoassay for rotavirus antigen, followed by polymerase chain reaction verification of antigen detection. Results A total of 3705 AGE case patients and 1563 HCs were enrolled, among whom 2885 case patients (78%) and 1110 HCs (71%) provided stool specimens that were tested. All 4 viruses were more frequently detected in AGE case patients than in HCs (norovirus, 22% vs 8%, respectively; rotavirus, 10% vs 1%; sapovirus, 10% vs 5%; and astrovirus, 5% vs 2%; P  < .001 for each virus). In the OP setting, rates of AGE due to norovirus were higher than rate for the other 3 viruses. Children <5 years old had higher OP AGE rates than older children for all viruses. Conclusions Norovirus remains the most common virus detected in all settings, occurring nearly twice as frequently as the next most common pathogens, sapovirus and rotavirus. Combined, norovirus, sapovirus, rotavirus, and astrovirus were associated with almost half of all AGE visits and therefore are an important reason for children to receive medical care. [ABSTRACT FROM AUTHOR]

A time series analysis of 871 543 pediatric emergency visits revealed that the coronavirus disease 2019 (COVID-19) lockdown and school closures were associated with a significant decrease in infectious diseases disseminated through airborne or fecal–oral transmission: common cold, gastroenteritis, bronchiolitis, and acute otitis. No change was found for urinary tract infections. [ABSTRACT FROM AUTHOR]

The proportion of sinusitis visits that meet antibiotic prescribing criteria is unknown. Of 425 randomly selected sinusitis visits, 50% (214) met antibiotic prescribing criteria. There was no significant difference in antibiotic prescribing at visits that did (205/214 [96%]) and did not (193/211 [92%]; P  = .07) meet antibiotic prescribing criteria. [ABSTRACT FROM AUTHOR]

Background Establishment of persistent human immunodeficiency virus type 1 (HIV-1) reservoirs occurs early in infection, and biomarkers of infected CD4+ T cells during acute infection are poorly defined. CD4+ T cells expressing the gut homing integrin complex α4β7 are associated with HIV-1 acquisition, and are rapidly depleted from the periphery and gastrointestinal mucosa during acute HIV-1 infection. Methods Integrated HIV-1 DNA was quantified in peripheral blood mononuclear cells obtained from acutely (Fiebig I–III) and chronically infected individuals by sorting memory CD4+ T-cell subsets lacking or expressing high levels of integrin β7 (β7negative and β7high, respectively). HIV-1 DNA was also assessed after 8 months of combination antiretroviral therapy (cART) initiated in Fiebig II/III individuals. Activation marker and chemokine receptor expression was determined for β7-defined subsets at acute infection and in uninfected controls. Results In Fiebig I, memory CD4+ T cells harboring integrated HIV-1 DNA were rare in both β7high and β7negative subsets, with no significant difference in HIV-1 DNA copies. In Fiebig stages II/III and in chronically infected individuals, β7high cells were enriched in integrated and total HIV-1 DNA compared to β7negative cells. During suppressive cART, integrated HIV-1 DNA copies decreased in both β7negative and β7high subsets, which did not differ in DNA copies. In Fiebig II/III, integrated HIV-1 DNA in β7high cells was correlated with their activation. Conclusions β7high memory CD4+ T cells are preferential targets during early HIV-1 infection, which may be due to the increased activation of these cells. [ABSTRACT FROM AUTHOR]

Background Clinicians cannot reliably predict complications of acute hematogenous osteomyelitis (AHO). Methods Consecutive cases of AHO from 2 pediatric centers in the United States were analyzed retrospectively to develop clinical tools from data obtained within 96 hours of hospitalization to predict acute and chronic complications of AHO. Two novel composite prediction scores derived from multivariable logistic regression modeling were compared with a previously published severity of illness (SOI) score, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) using area under the receiver operating characteristic curve analyses. Results The causative organisms were identified in 73% of 261 cases. Bacteremia (45%), abscesses (38%), and associated suppurative arthritis (23%) were relatively common. Acute or chronic complications occurred in 24% and 11% of patients, respectively. Multivariable logistic regression identified bone abscess (odds ratio [OR], 2.3 [95% confidence interval {CI}, 1.0–5.2]), fever > 48 hours (OR, 2.7 [95% CI, 1.2–6.0]), suppurative arthritis (OR, 3.2 [95% CI, 1.3–7.5]), disseminated disease (OR, 4.6 [95% CI, 1.5–14.3]), and delayed source control (OR, 5.1 [95% CI, 1.4–19.0]) as strong predictors of acute complications. In a separate model, CRP ≥ 100 mg/L at 2–4 days after antibiotics (OR, 2.7 [95% CI, 1.0–7.3]), disseminated disease (OR, 3.3 [95% CI, 1.1–10.0]), and requirement for bone debridement (OR, 6.7 [95% CI, 2.1–21.0]) strongly predicted chronic morbidity. These variables were combined to create weighted composite prediction scores for acute (A-SCORE) and chronic (C-SCORE) osteomyelitis, which were superior to SOI, CRP, and ESR and had negative predictive values > 90%. Conclusions Two novel composite clinical scores were superior to existing tools to predict complications of pediatric AHO. [ABSTRACT FROM AUTHOR]

Background Since 2006, the New Vaccine Surveillance Network has conducted active, population-based surveillance for acute gastroenteritis (AGE) hospitalizations and emergency department (ED) visits in 3 United States counties. Trends in the epidemiology and disease burden of rotavirus hospitalizations and ED visits were examined from 2006 to 2016. Methods Children < 3 years of age hospitalized or visiting the ED with AGE were enrolled from January 2006 through June 2016. Bulk stool specimens were collected and tested for rotavirus. Rotavirus-associated hospitalization and ED visit rates were calculated annually with 2006–2007 defined as the prevaccine period and 2008–2016 as the postvaccine period. Rotavirus genotype trends were compared over time. Results Over 11 seasons, 6954 children with AGE were enrolled and submitted a stool specimen (2187 hospitalized and 4767 in the ED). Comparing pre- and postvaccine periods, the proportion of children with rotavirus dramatically declined for hospitalization (49% vs 10%) and ED visits (49% vs 8%). In the postvaccine era, a biennial pattern of rotavirus rates was observed, with a trend toward an older median age. G1P[8] (63%) was the predominant genotype in the prevaccine period with a significantly lower proportion (7%) in the postvaccine period (P  < .001). G2P[4] remained stable (8% to 14%) in both periods, whereas G3P[8] and G12P[8] increased in proportion from pre- to postvaccine periods (1% to 25% and 17% to 40%), respectively. Conclusions The epidemiology and disease burden of rotavirus has been altered by rotavirus vaccination with a biennial disease pattern, sustained low rates of rotavirus in children < 3 years of age, and a shift in the residual genotypes from G1P[8] to other genotypes. [ABSTRACT FROM AUTHOR]

An adult male from Missouri sought care for fever, fatigue, and gastrointestinal symptoms. He had leukopenia and thrombocytopenia and was treated for a presumed tickborne illness. His condition deteriorated with respiratory and renal failure, lactic acidosis, and hypotension. Next-generation sequencing and phylogenetic analysis identified a reassortant Cache Valley virus. [ABSTRACT FROM AUTHOR]

Background Men who have sex with men (MSM) are at risk for sexual transmission of enteric pathogens. The microbiology of gastroenteritis in MSM has not been examined since the advent of antiretroviral therapy and molecular diagnostics. Our objective was to assess the causes of gastroenteritis among MSM living with and without human immunodeficiency virus (HIV) coinfection in Seattle, Washington. Methods We conducted a retrospective cohort study of 235 MSM who underwent multiplex stool polymerase chain reaction (PCR) testing between 1 January 2017 and 1 June 2018. We abstracted clinical and laboratory data from electronic medical records. Parallel or reflexive culture and susceptibility testing were performed when PCR detected cultivable pathogens. Results Among 235 MSM tested (268 episodes), 131 had 151 episodes with positive test results. 148 (63.0%) individuals were living with HIV. Among positive tests, 88.7% detected a bacterial pathogen, 26% a virus, and 40% a parasite. Diarrheagenic Escherichia coli (enteroaggretative, enteropathogenic), Shigella , and Campylobacter were the most commonly detected bacteria (33.1%, 30.5%, and 17.2% of positive samples, respectively). Forty-three percent of positive specimens had ≥2 pathogens. Etiologies and clinical presentations were similar between men living with and without HIV. Cultured Shigella and Campylobacter isolates were frequently resistant to multiple antibiotics. Conclusions MSM present with gastroenteritis from varied pathogens, including some not detected by conventional stool culture. High levels of antibiotic resistance are consistent with frequent antibiotic exposure in this population and the transmission of multiresistant strains. New approaches are needed to detect, treat, and prevent enteric infections in MSM. [ABSTRACT FROM AUTHOR]

Background Beginning from 2015–2016, unprecedented large outbreaks of acute hepatitis A that predominantly affected men who have sex with men (MSM) reemerged across the continents. We assessed the impact of an early initiated hepatitis A virus (HAV) vaccination campaign that targeted MSM living with human immunodeficiency virus (HIV) during the 2015–2017 hepatitis A outbreak in Taiwan. Methods First, we ascertained the effectiveness of HAV vaccination for MSM living with HIV using a nested case-control study of 1470 persons living with HIV who were initially HAV-seronegative. We then fitted a model of HAV transmission among MSM, risk-structured by HIV status, to the actual epidemic curve of reported acute hepatitis A cases in Taiwan during 2015–2017. Results Fifty-five cases of acute hepatitis A were matched to 220 controls. Single-dose and 2-dose HAV vaccination provided protection rates of 96.1% and 97.8% among recipient MSM living with HIV, respectively. Model fitting yielded basic reproductive number estimates of 7.26 (MSM living with HIV) and 3.04 (MSM not living with HIV). In a counterfactual scenario without an HAV vaccination campaign, the outbreak would have involved 7153 hepatitis A cases during 2015–2017 in contrast to the 1352 that were observed. We therefore estimated that the HAV vaccination campaign averted 80.7% (sensitivity analysis, 48.8%–92.7%) of acute hepatitis A cases that would otherwise have occurred by the end of 2017. Conclusions The early initiated HAV vaccination campaign, which targeted MSM living with HIV, very effectively curtailed the 2015–2017 hepatitis A outbreak in Taiwan. [ABSTRACT FROM AUTHOR]

Background Effective therapeutics for respiratory viruses are needed. Early data suggest that nitazoxanide (NTZ) may be beneficial for treating acute respiratory viral illness. Methods From March 2014 through March 2017, a double-blind, placebo-controlled trial was conducted in 260 participants ≥1 year old hospitalized with influenza-like illness at 6 hospitals in Mexico. Participants were randomized 1:1 to NTZ (age ≥12 years, 600 mg twice daily; age 4–11 years and 1–3 years, 200 or 100 mg twice daily, respectively) or placebo for 5 days in addition to standard of care. The primary endpoint was time from first dose to hospital discharge. Influenza reverse-transcription polymerase chain reaction and Respifinder 22 multiplex test were used for virus detection. Results Of 260 participants enrolled, 257 were randomized and took at least 1 dose of study treatment (intention-to-treat population): 130 in the NTZ group and 127 in the placebo group. The Kaplan-Meier estimate of the median duration of hospitalization was 6.5 (interquartile range [IQR], 4.0–9.0) days in the NTZ group vs 7.0 (IQR, 4.0–9.0) days in the placebo group (P =.56). Duration of hospitalization between the 2 treatments was similar in children (P =.29) and adults (P =.62), influenza A and B (P =.32), and other respiratory viruses. Seven (5.4%) and 6 (4.7%) participants in the NTZ and placebo groups, respectively, reported serious adverse events. Conclusions Treatment with NTZ did not reduce the duration of hospital stay in severe influenza-like illness. Further analyses based on age and evaluations by virus did not reveal any subgroups that appeared to benefit from NTZ. Clinical Trials Registration NCT02057757. [ABSTRACT FROM AUTHOR]

Background We examined the impact of vancomycin-resistant Enterococcus (VRE) bloodstream infection (BSI) on outcomes of allogeneic hematopoietic cell transplantation (HCT) utilizing the Center for International Blood and Marrow Transplant Research database. Methods Adult and pediatric patients (N = 7128) who underwent first HCT for acute leukemia or myelodysplastic syndrome from 2008 through 2012 were analyzed as 3 groups—VRE BSI, non-VRE BSI, without BSI—according to BSI status at 100 days (D100) after allogeneic HCT. Multivariable models examined the effect of VRE BSI for overall survival (OS) and nonrelapse mortality (NRM) at 1 year. Results Of 7128 patients, 258 (3.2%) had VRE BSI, 2398 (33.6%) had non-VRE BSI, and 4472 (63%) had no BSI. The median time to VRE BSI and non-VRE BSI were D11 and D15, respectively. Compared with non-VRE BSI patients, VRE BSI patients were older, had advanced-stage acute leukemia, and received umbilical cord blood (UCB) allografts. In multivariable models, VRE BSI was associated with lower OS (relative risk [RR], 2.9;(99% confidence interval [CI], 2.2–3.7) and increased NRM (RR, 4.7; 99% CI, 3.6–6.2) (P <.0001) for both. Other predictors for worse OS and increased NRM were non-VRE BSI, older age, advanced disease stage, UCB allograft, – mismatch, comorbidity index ≥3, and cytomegalovirus seropositivity (P <.001 for all variables). Conclusions VRE BSI is associated with lowest OS and highest NRM compared with patients without BSI or non-VRE BSI. Novel interventions that address the pathophysiology of VRE BSI have the potential of improving survival after HCT. [ABSTRACT FROM AUTHOR]

Background Acute bacterial sinusitis is a frequent complication of viral upper respiratory infection (URI). We describe the clinical and virologic features of URIs that remain uncomplicated and those that precede an episode of sinusitis. We hypothesize that certain viruses are more likely to lead to acute sinusitis, and we compare viruses identified at the time of diagnosis of sinusitis with those identified early in the URI. Methods Children aged 48–96 months were followed longitudinally for 1 year. Nasal samples were obtained at surveillance visits, on Day 3–4 of the URI, and on Day 10, when sinusitis was diagnosed. Molecular diagnostic testing was performed on nasal washes for common respiratory viruses and pathogenic bacteria. A standardized score was used to quantify symptom severity. Results We evaluated 519 URIs, and 37 illnesses in 31 patients met the criteria for sinusitis. Respiratory syncytial virus was detected more frequently in URI visits that led to sinusitis, compared to in uncomplicated URIs (10.8% vs 3.4%; P =.05). New viruses were detected in 29% of sinusitis episodes, and their pattern was different than those patterns observed at surveillance. The median number of URIs per subject per year was 1 (range 0–9) in uncomplicated URI subjects and 3 (range 1–9) in sinusitis subjects (P <.001). Conclusions Children who developed sinusitis experienced more frequent URIs, compared to children whose URIs remained uncomplicated. When nasal samples were obtained on the day of diagnosis of acute sinusitis, nearly 30% of children had a new virus identified, suggesting that some children deemed to have sinusitis were experiencing sequential viral infections. [ABSTRACT FROM AUTHOR]

Background The early detection of enteric infections in older adults is challenging because typical signs and symptoms of disease may be less common, absent, or overlooked. Understanding illness characteristics of enteric infections among older adults could improve the timeliness and accuracy of clinical diagnoses, thereby improving patient outcomes and increasing cases reported to surveillance. Methods Here, we describe illness characteristics (percentage reporting bloody diarrhea, fever, vomiting, abdominal pain; percentage hospitalized; duration of hospitalization; and duration of illness) among older adults (≥65 years) with acute gastroenteritis and culture-confirmed Campylobacter and nontyphoidal Salmonella infections in Australia, Canada, and the United States and compare these characteristics with those among younger people (<5 years, 5–24 years, and 25–64 years). Results A significant negative correlation was found between all symptoms and increasing age group, except for bloody diarrhea in cases of acute gastroenteritis. Adults aged ≥85 years reported bloody diarrhea in only 9% of nontyphoidal Salmonella and 4% of Campylobacter infections compared with 59% and 55% among children aged <5 years. Conversely, a greater percentage of older adults (≥65) than younger persons (<5, 5–24, 25–64) reported being hospitalized, with an increasing linear relationship in age groups 65 years and older. Conclusions Although older adults are more likely to have severe illness and be hospitalized, we found that the proportion of persons reporting symptoms typically associated with enteric infections decreases with age. These findings have implications for clinical recognition and treatment of gastrointestinal illness, as well as for public health research. [ABSTRACT FROM AUTHOR]