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Background Families with children may be at higher risk for influenza infection. Community transmission can suffer from underreporting as testing is often not performed. We studied the epidemiology of influenza in households with school-aged children using home-based sample collection. Methods We conducted a remote household study surveilling respiratory viruses from November 2019-June 2021, in King County, Washington (WA), USA. Households with school-aged children were enrolled, mailed home specimen collection kits, and asked to self-assess for weekly acute respiratory illness (ARI) using remote survey platforms. Participants with ARI symptoms were prompted to complete serial illness surveys and self-collect/parent collect mid-turbinate nasal swabs. Samples were sent to a University of Washington study laboratory for RT-PCR influenza testing. Influenza rates were compared to WA Department of Health (DOH) reporting. Results A total of 1861 ARI events were reported among 992 adults and 869 children in 470 households; 75 influenza cases were detected (36 influenza A and 39 influenza B). The study participant median age was 32 years (0-84), 10 years (1-49) for influenza A, and 11 years (3-49) for influenza B cases. Overall 13% of households had an influenza case, of which 13 (22%) reported >1 case. A total of 81% of participants reported receipt of one dose of the 2019-2020 influenza vaccine, including 91% of influenza A and 90% of influenza B cases, and 84% received the 2020-2021 influenza vaccine. Like WA DOH, we observed a wave of influenza B cases followed by influenza A in 2019-2020. During influenza season 2020-2021, WA DOH reported 9 positive influenza tests and none observed in our study. Commonly, influenza case-patients reported were fever, cough, rhinorrhea, and fatigue. GI symptoms were more common in children than adults. Of the cases, 92% of influenza A and 78% of influenza B occurred in children. Figure 1.Influenza A and B cases from 2019-2021Figure 2A.Reported Symptoms of Influenza A D0-Day of reported onset, D7-7 days after reported illness onset. No participants >49 years were positive for influenza. D0: 30 participants responded and of respondents, 13% D0-Day of reported onset, D7-7 days after reported illness onset. No participants >49 years were positive for influenza. D0: 28 participants responded and of respondents, 4% Conclusion Influenza illness in 2019-2020 was initially influenza B, and subsequently replaced by influenza A. Most cases were in children and adolescents, despite at least one dose of influenza vaccine. Symptoms were widely distributed and similar between influenza A and B. Influenza incidence in our cohort declined to zero with the rise of SARS-CoV-2 cases and widespread mitigation efforts. Disclosures Janet A. Englund, MD, AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Meissa Vaccines: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant Helen Y. Chu, MD, MPH, Cepheid: Reagents|Ellume: Advisor/Consultant|Gates Ventures: Grant/Research Support|Merck: Advisor/Consultant|Pfizer: Advisor/Consultant.

Background COVID-19 vaccines are important to mitigate severe disease in congregate settings, yet uptake remains lower among people experiencing homelessness (PEH) than in the general population. This study aimed to explain changes in COVID-19 vaccination intent over time and identify modifiable factors to improve vaccine acceptance among PEH. Methods We utilized the Health Belief Model and 3Cs Model of Vaccine Hesitancy to develop a conceptual framework to explore factors that may influence COVID-19 vaccination intent among PEH. Between July 27 - October 15, 2021, we conducted semi-structured interviews (SSIs) and focus group discussions (FGDs) across six homeless shelters in Seattle-King County, Washington. Residents and staff aged 18 years and older were recruited through purposive sampling for SSIs and convenience sampling for FGDs. We captured retrospective information about perceptions of and intent to receive COVID-19 vaccines between March 2020 - August 2021. Thematic analysis was conducted using Dedoose. Results We conducted 31 SSIs (25 residents and six staff) and eight FGDs with 43 residents. Participants reported that too much contradictory and changing information about COVID-19 vaccines led to confusion. Information deemed trustworthy (i.e., objective, honest, professional, and recommended by others) contributed to individual’s knowledge and in some cases changed their vaccination intent. Despite intention to vaccinate, participants reported barriers to COVID-19 vaccine access including availability, eligibility, appointments, and timeliness. While many intended to get vaccinated on their own, others were motivated by incentives and requirements. Participants presented recommendations to improve COVID-19 information content and dissemination, access, and incentives in shelter settings (Table 1). Table 1.Recommendations for Interventions to Increase COVID-19 Vaccine Uptake in Shelter Settings Conclusion COVID-19 vaccination strategies that are rooted in the voices and experiences of PEH are presented and can inform improved vaccine implementation among key stakeholders. Future research should test recommended strategies to determine feasibility and effectiveness in shelter settings. Disclosures Helen Y. Chu, MD, MPH, Cepheid: Reagents|Ellume: Advisor/Consultant|Gates Ventures: Grant/Research Support|Merck: Advisor/Consultant|Pfizer: Advisor/Consultant.

Background Non-pharmaceutical interventions (NPIs), such as masking and social distancing, can reduce SARS-CoV-2 transmission. Longitudinal behavioral data in individuals with acute respiratory illness (ARI) during the COVID-19 pandemic are limited. We describe changes in adherence to NPIs and the impact of ARIs on work or school in families before and during the COVID-19 pandemic. Methods From November 2019 to June 2021, households with school-aged children in King County, WA, were remotely monitored on a weekly basis for symptoms of respiratory illness. Participants with ARI (cough or ≥2 qualifying symptoms) were asked about illness-related behavior changes (e.g. masking, isolation, hand hygiene, surface cleaning, public transit use) and impacts on school/work 7 days after initial symptom report. Using generalized estimating equations for household clusters, we compared the frequency of behavior changes and school/work impact during 3 time periods: the pre-/early COVID-19 pandemic period (11/14/19-3/22/20), pre-vaccine period (3/23/20-12/10/20), and post-COVID-19 vaccine period (12/11/20-6/19/21). Results Of 1861 participants in 470 households, 695 (37%, from 70% of households) reported 1157 ARIs. Over the 3 time periods, the percent of ill participants who reported staying home (34 vs 34 vs 54%, respectively, P< .001), avoiding contact with others (25 vs 28 vs 45%, P< .001), and masking (3 vs 23 vs 38%, P< .001) increased (Fig 1A). Other illness-related behaviors, including washing hands and disinfecting surfaces, were unchanged over time. The percent of ill participants who worked from home (7 vs 9 vs 3%, P= .02) and missed work due to ARI (13 vs 8 vs 8%, P= .03) decreased over time (Fig 1B). Figure 1A.Participant reported illness-related health behaviors in the past week — Seattle, WA, 2019–2021.Figure 1B.Participant reported illness-related school or work impact in the past week due to illness — Seattle, WA, 2019–2021 Time periods were defined as: Period 1: 11/14/19 – 3/22/20 (pre-/early COVID-19 pandemic), Period 2: 3/23/20 – 12/10/20 (post-Washington State Stay at Home order), and Period 3: 12/11/20 – 6/19/21 (United States Food and Drug Administration Emergency Use Authorization for the Pfizer-BioNTech COVID-19 vaccine for those 16 years and older). Illness was defined per Acute Respiratory Illness (ARI) case definition: cough or two qualifying symptoms (fever, sore throat, runny nose, muscle or body aches, headache, difficulty breathing, fatigue, nausea or vomiting; for participants < 18 years of age, ear pain or drainage, rash, and diarrhea were also qualifying symptoms). Conclusion As the COVID-19 pandemic progressed, households with school-aged children engaged in isolation, social distancing, and masking more frequently in response to ARI. The impact of ARIs on work decreased during the pandemic. Disclosures Janet A. Englund, MD, AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Meissa Vaccines: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant Helen Y. Chu, MD, MPH, Cepheid: Reagents|Ellume: Advisor/Consultant|Gates Ventures: Grant/Research Support|Merck: Advisor/Consultant|Pfizer: Advisor/Consultant.

Background Human parainfluenza viruses (HPIV) cause respiratory illness in individuals of all ages. However, HPIV epidemiology data in people experiencing homelessness (PEH) are limited. Methods We analyzed cross-sectional data from a clinical trial and SARS-CoV-2 surveillance study in 23 homeless shelters in King County, Washington from October 2019-May 2021. Questionnaires and nasal swab specimens were obtained from eligible participants at enrollment. Between October 2019-March 31, 2020, participants included those aged > 3 months with acute respiratory illness. Monthly shelter surveillance was also conducted where participants were recruited regardless of symptoms. With the community spread of SARS-CoV-2, the study design transitioned from a clinical trial to a SARS-CoV-2 surveillance study which expanded enrollment eligibility to include participants with or without symptoms from April 1, 2020, onward. Participants were not followed longitudinally but were permitted to enroll multiple times during the study period. Specimens were tested for HPIV 1-4 and other respiratory viruses using RT-PCR. Results Among 14,464 specimens, 32 were HPIV-positive from 29 participants (median age 9 years, range 0.3-64 years; 45% female; 28% Black; 10% with chronic conditions) of which 59% were children. Family shelters had the highest percentage of HPIV infections (Table). HPIV was detected every month before the community spread of SARS-CoV-2. All HPIV-positive samples in May 2021 came from a single family shelter (Figure). Only 67% of HPIV-positive participants had symptoms with runny nose, cough and sore throat the most commonly reported. HPIV co-detection with other respiratory viruses occurred in 19% of HPIV-positive specimens; Rhinovirus co-detection (16%) was the most common. Human Parainfluenza Encounters by Shelter Type Before and After April 1, 2020 Human Parainfluenza Positive Samples by Shelter Type Among Unique Participants Conclusion HPIV affected PEH of all ages with most cases in shelters with children. Coinciding with community-wide SARS-CoV-2 mitigation efforts, the number of HPIV infections were reduced. However, a cluster of HPIV infections still occurred within one family shelter. Shelter-specific public health measures including non-pharmaceutical interventions used during the COVID-19 pandemic may reduce HPIV infections among residents. Disclosures Janet A. Englund, MD, AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Meissa Vaccines: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant Helen Y. Chu, MD, MPH, Cepheid: Reagents|Ellume: Advisor/Consultant|Gates Ventures: Grant/Research Support|Merck: Advisor/Consultant|Pfizer: Advisor/Consultant.

Background Households are common places for spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We investigated factors associated with household transmission and acquisition of SARS-CoV-2. Methods Households with children age Results Among 2053 people (513 households) enrolled, 180 people (8.8%; in 76 households) tested positive for SARS-CoV-2. Compared with children age Conclusions Adults had lower odds of acquiring SARS-CoV-2 compared with children, but this association might be influenced by coronavirus disease 2019 (COVID-19) vaccination, which was primarily available for adults and protective against infection. In contrast, all ages, regardless of symptoms and COVID-19 vaccination, had similar odds of transmitting SARS-CoV-2. Our findings underscore the importance of SARS-CoV-2 mitigation measures for persons of all ages.

Background Anterior nasal swabs (ANS) are established specimen collection methods for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection detection. While saliva (SA) specimens provide an alternative, few studies have comprehensively characterized the performance of SA specimens in longitudinal studies. Methods We compared SARS-CoV-2 detections between paired self-collected ANS and SA specimens from a household transmission study. Participants recorded symptoms and paired ANS and SA specimens daily for 14 days. Specimens were tested using RT-PCR. We calculated the proportion of detections identified by each specimen type among the detections from both types combined. We computed percent agreement and Kappa statistics to assess concordance in detections. We also computed estimates stratified by presence of symptoms and examined the influence of traditional and inactivating transport media on the performance of ANS. Results We examined 2535 self-collected paired specimens from 216 participants. Among 1238 (49%) paired specimens with detections by either specimen type, ANS identified 77.1% (954; 95% CI, 74.6% to 79.3%) and SA 81.9% (1014; 95% CI, 79.7% to 84.0%), with a difference of 4.9% (95% CI, 1.4% to 8.5%). Overall agreement was 80.0%, and Kappa was 0.6 (95% CI, 0.5 to 0.6). Nevertheless, the difference in the proportion of detections identified by ANS and SA using traditional and inactivating transport media was 32.5% (95% CI, 26.8% to 38.0%) and –9.5% (95% CI, −13.7% to –5.2%), respectively. Among participants who remained asymptomatic, the difference in detections between SA and ANS was 51.2% (95% CI, 31.8% to 66.0%) and 26.1% (95% CI, 0% to 48.5%) using traditional and inactivating media, respectively. Conclusions Self-collected saliva specimens provide a noninvasive alternative to nasal swabs, especially to those collected in traditional transport media, for longitudinal field studies that aim to detect both symptomatic and asymptomatic SARS-CoV-2 infections.

Background Shortages of swabs and transport medium for sample collection have made identification of SARS-CoV-2 infections challenging. We examined the agreement in SARS-CoV-2 detection between two types of self-collected samples: nasal swabs (NS) and saliva (SA). Figure 1. Bland-Altman plot of SARS-CoV-2-N1 CT values for SA and NS samples Figure 2. Bland-Altman plot of SARS-CoV-2-N2 CT values for SA and NS samples Methods Paired daily self-collected NS and SA samples were collected in May 2020 in an ongoing case-ascertained study of SARS-CoV-2 household transmission in Nashville, TN. After informed consent was obtained, index cases and household members were remotely trained in the self-collection of daily nasal swabs (from both nares and preserved in transport medium) and saliva samples (participants were asked to spit in a sterile urine cup approximately 6 times during a minute). Samples were refrigerated in closed double bags and delivered to the laboratory within ~72–96 hours of collection. NS and SA samples were tested using qRT-PCR at a research laboratory. We computed the agreement in detections between sample types using the McNemar test and compared median qRT-PCR cycle threshold (CT) values between sample types for 2 targets (SARS-CoV-2-N1 and SARS-CoV-2-N2) using a Wilcoxon signed rank test. Bland-Altman plots were used to visually inspect agreement between NS and SA CT values. Results Among 144 self-collected samples (72 pairs) from 13 unique participants (5 index cases and 8 household members), there were 30 pairs with concordant positive detections in both sample types, 35 with concordant negative detections in both samples, 1 pair with positive NS only, and 6 pairs with positive SA only. The overall agreement between NS and SA was 90.3% (p=0.1). The median SARS-CoV-2-N1 CT value for NS samples was 33.3 (interquartile range: 30.2–35.3) and for SA samples was 30.5 (29.8–33.3, p=0.04); the median CT value for SARS-CoV-2-N2 was 34.4 (31.5–37.5) and 31.5 (30.4–34.9), respectively (p=0.01). Bland-Altman plots indicated that most observations were contained within the limits of agreement but suggested NS tended to have higher CT values than SA samples (Figures). Conclusion Self-collection of saliva samples provides a simple, non-invasive, and practical strategy for identification of SARS-CoV-2 infections. Disclosures Carlos G. Grijalva, MD, MPH, AHRQ (Grant/Research Support)Campbell Alliance (Grant/Research Support)CDC (Grant/Research Support)FDA (Grant/Research Support)Merck (Consultant)NIH (Scientific Research Study Investigator)Pfizer (Consultant)Sanofi (Consultant)Sanofi (Grant/Research Support) Natasha B. Halasa, MD, MPH, Genentech (Other Financial or Material Support, I receive an honorarium for lectures - it’s a education grant, supported by genetech)Karius (Consultant)Moderna (Consultant)Quidel (Grant/Research Support, Research Grant or Support)Sanofi (Grant/Research Support, Research Grant or Support)

Background Social distancing measures, such as shelter-in-place or stay-at-home orders, are recommended for control of community transmission of SARS-CoV-2. Few studies, however, have characterized the transmission of SARS-CoV-2 infections in households. Methods We conducted a case-ascertained study of household transmission in Nashville, TN starting in April 2020, after recommendations to stay at home were enacted. Index cases were ambulatory patients identified through clinical RT-PCR testing at Vanderbilt walk-in-clinics dispersed across the Nashville metropolitan area. For this study, the index case was the first person presenting with respiratory or compatible symptoms in a household and who lived with at least one other household member. After informed consent was obtained, household members were remotely trained in the self-collection of nasal swabs and use of REDCap electronic questionnaires. Household members completed daily symptom diaries and collected daily nasal swabs for 14 days. Contact patterns within households before and after disease onset were ascertained. Nasal swab samples were tested using RT-PCR at an academic research laboratory. Results At the time of writing, 18 families were enrolled (including 18 index cases and 34 household members) with at least 1 follow-up nasal swab tested. The median age of index cases and household members was 37 years (IQR: 26–46) and 27 years (15–39), respectively. The median number of days from index patient onset of symptoms to first sample collected in the household was 4 (2–5). Before onset of symptoms, 83% of index cases spent >4 hours in the same room with at least one other household member, whereas after disease onset and diagnosis, 44% did. Among 34 non-index household members, 18 (53%) had a positive test during follow-up; the median number of days from index case’s symptoms onset to first positive detection in a household member was 4.5 (3–5) days. Interestingly, 13 (72%) of 18 secondary infections were detected within the first 3 days of follow-up, whereas 5 (28%) were detected during subsequent days. Conclusion These observations suggest that transmission of SARS-CoV-2 within households is high, with many infections detected during the initial days of study follow-up. Disclosures Carlos G. Grijalva, MD, MPH, AHRQ (Grant/Research Support)Campbell Alliance (Grant/Research Support)CDC (Grant/Research Support)FDA (Grant/Research Support)Merck (Consultant)NIH (Scientific Research Study Investigator)Pfizer (Consultant)Sanofi (Consultant)Sanofi (Grant/Research Support) Natasha B. Halasa, MD, MPH, Genentech (Other Financial or Material Support, I receive an honorarium for lectures - it’s a education grant, supported by genetech)Karius (Consultant)Moderna (Consultant)Quidel (Grant/Research Support, Research Grant or Support)Sanofi (Grant/Research Support, Research Grant or Support)

Background Influenza virus infection most commonly causes acute respiratory tract illness, however may also lead to non-respiratory complications including acute cardiovascular (CV) events. We describe the frequency of and risk factors for acute CV events in adults hospitalized with influenza in the United States. Methods We included adults aged > 18 years hospitalized during influenza seasons 2010–2011 through 2017–2018 in FluSurv-NET, a multi-state population-based surveillance system that includes detailed medical chart review of patients hospitalized with laboratory-confirmed influenza. We defined acute CV events by International Classification of Diseases (ICD) primary and secondary discharge diagnosis codes for acute heart failure (aHF), acute ischemic heart disease (aIHD), hypertensive crisis, cardiogenic shock, acute myocarditis, acute pericarditis and cardiac tamponade. We calculated the frequency of acute CV events and used multivariable logistic regression among the 87% treated with influenza antivirals to identify independent factors associated with aHF and aIHD, the two most common diagnoses. Results Of 80,374 adults hospitalized with laboratory-confirmed influenza, 12% had > 1 acute CV event. We found that aHF (46%) and aIHD (42%) were the most common, followed by hypertensive crisis (8%), cardiogenic shock (3%), acute myocarditis (0.7%), acute pericarditis (0.4%) and cardiac tamponade (0.2%). Compared with treated patients without an acute cardiovascular event, treated patients with aHF (Figure A) and aIHD (Figure B) were more likely to be older, currently/formerly use tobacco and have underlying conditions including cardiovascular disease, diabetes mellitus, and kidney disease. Conclusion Among adults hospitalized with laboratory-confirmed influenza, acute CV events are common, particularly among those with prior cardiovascular disease. During the influenza season, clinicians should consider influenza virus infection in hospitalized adults who present with acute CV events. Non-respiratory complications, specifically aHF and aIHD, may be an under-recognized contributor to the burden of influenza. Disclosures All authors: No reported disclosures.

Background Few studies have quantified the risk of community-acquired pneumonia (CAP) among adults with co-morbidities. Combining data from the population-based, prospective Etiology of Pneumonia in the Community study (EPIC) and the nationwide health-related Behavioral Risk Factor Surveillance System (BRFSS) telephone-survey, we estimated the annual risk of hospitalization for CAP among adults with co-morbidities. Methods We identified adults hospitalized with radiographic and clinical CAP at hospitals in Chicago, IL and Nashville, TN from July 2010 to June 2012. Using 2011 BRFSS data, we estimated the prevalence of the population with selected co-morbidities (chronic lung disease [CLD], cardiovascular disease [CVD], chronic kidney disease [CKD], or diabetes) in the EPIC study catchment counties, as well as the population without co-morbidities. We estimated the incidence of hospitalized CAP, age-adjusted relative risk (RR) using Poisson regression, and population attributable fraction for each co-morbidity. Results Among 2,061 adult patients enrolled in EPIC, 1,428 (69%) had at least one selected co-morbidity, most commonly CLD (42%) and CVD (35%). Among the adult population in the EPIC catchment area, 17% had ≥1 selected co-morbidity. The overall incidence of hospitalized CAP was 24.8/10,000, 118.7/10,000 among adults with ≥1 co-morbidity, and 11.2/10,000 among adults without a co-morbidity. Compared with patients without co-morbidities, the incidence of hospitalization for CAP was higher among patients with CLD (aRR: 20.7 [95% confidence interval [CI]: 20.0–21.5]), CKD (aRR: 14.5 [CI: 13.8–15.1]), CVD (aRR: 14.0 [CI: 13.5–14.6]), and diabetes (aRR: 6.2 [CI: 5.9–6.4]). While CLD and CVD accounted for high proportions of the incidence of CAP hospitalizations in the study population, the contribution of the selected co-morbidities varied by age groups (figure). Conclusion There is an increased risk of hospitalization for CAP among adults with co-morbidities, particularly chronic lung and cardiovascular disease. As a large portion of CAP is attributable to these co-morbidities, targeted public health interventions, such as vaccination and risk communication, need to be reinforced among these high-risk groups. Disclosures All authors: No reported disclosures.

Background Few data describe the epidemiology of influenza among adults ≥65 years old according to age strata. We evaluated age-related differences in influenza-associated hospitalization rates, clinical presentation, and outcomes among older adults at 14 FluSurv-NET sites during the 2011–2012 through 2014-2015 influenza seasons. Methods Study patients were hospitalized ≤14 days after and ≤3 days before a positive influenza test. Age strata were 65–74, 75–84, and ≥85 years old. We adjusted hospitalization rates for under detection and assessed for age-related trends in risk factors and symptoms. We used logistic regression to calculate odds ratios (OR) for pneumonia and in-hospital death adjusted for season, sex, nursing home residence, smoking, medical comorbidities, influenza vaccination, and study site. Results There were 19,760 patients, including 5,956 aged 65–74 years, 6,998 aged 75–84 years, and 6,806 aged ≥85 years. There was a stepwise increase in hospitalization rates with age (figure). Increasing age was positively associated with female sex, nursing home residence, neurologic disorder, cardiovascular and renal disease, and vaccination, and inversely associated with morbid obesity, smoking, asthma, chronic metabolic disease, and immunosuppression (P < 0.01). Among 10,548 (53.3%) patients with symptom data from 2014 to 2015, increasing age was associated with a higher prevalence of altered mental status and lower prevalence of fever, myalgias, respiratory or gastrointestinal symptoms, and headache (P ≤ 0.01). Compared with 65–74 year olds, older patients had a higher risk of pneumonia (≥85 year-olds: OR 1.2, 95% CI 1.0, 1.3, P = 0.01) and death (75–84 year olds: OR 1.4, 95% CI 1.2, 1.7, P < 0.01; ≥85 year-olds: OR 2.1, 95% CI 1.7, 2.6, P < 0.01). Conclusion There are age-related differences in the epidemiology, clinical presentation, and outcomes of older adults hospitalized with influenza. These may reflect differences in health status and healthcare provider practice patterns. Public health epidemiologists should consider using additional age strata in ≥65 year-olds when analyzing influenza surveillance data. Clinicians should be aware that influenza among the oldest adults may present atypically and that mortality is increased. Disclosures E. J. Anderson, NovaVax: Grant Investigator, Research grant. Pfizer: Grant Investigator, Research grant. AbbVie: Consultant, Consulting fee. MedImmune: Investigator, Research support. PaxVax: Investigator, Research support. Micron: Investigator, Research support. W. Schaffner, Merck: Member, Data Safety Monitoring Board, Consulting fee. Pfizer: Member, Data Safety Monitoring Board, Consulting fee. Dynavax: Consultant, Consulting fee. Seqirus: Consultant, Consulting fee. SutroVax: Consultant, Consulting fee. Shionogi: Consultant, Consulting fee.

We examined respiratory viral testing and influenza antiviral prescriptions at a US tertiary care hospital. During the 2010–11 to 2012–13 influenza seasons, antiviral prescriptions among acute respiratory illness (ARI) hospitalizations were associated with viral testing (rate ratio = 15.0), and empiric prescriptions were rare (

Capsule shedding in cerebrospinal fluid is associated with inflammatory and Th2-mediated immune responses in HIV-infected individuals with cryptococcal meningitis. These findings provide important insight into the interactions that occur between the host immune system and the infecting strain of Cryptococcus., Background. Cerebrospinal fluid (CSF) cryptococcal glucuronoxylomannan antigen (CrAg) titers generally correlate with quantitative fungal culture burden; however, correlation is not precise. Some patients have higher CrAg titers with lower fungal burdens and vice versa. We hypothesized that the relative discordancy between CrAg titer and quantitative culture burden reflects the relative degree of CrAg shedding by Cryptococcus neoformans and is associated with human immune responses. Methods. One hundred ninety human immunodeficiency virus-infected individuals with cryptococcal meningitis were enrolled in Uganda and South Africa. We compared initial CSF CrAg titers relative to their CSF quantitative cultures to determine low (n = 58), intermediate (n = 68), or high (n = 64) CrAg shedders. We compared cytokines measured by Luminex multiplex assay on cryopreserved CSF and 10-week mortality across shedding groups using linear and logistic regression and distribution of genotypes by multilocus sequence typing. Results. The relative degree of CrAg shedding was positively associated with increasing CSF levels of the following: interleukin (IL)-6, IL-7, IL-8, and tumor necrosis factor-α (each P < 0.01), which are all secreted by antigen-presenting cells and negatively associated with vascular endothelial growth factor (P = .01). In addition, IL-5, IL-13, granulocyte colony-stimulating factor, and macrophage chemotactic protein were decreased in low-CrAg shedders compared with intermediate shedders (each P ≤ .01). Type 1 T-helper cells (Th1) cytokine responses and 10-week mortality did not differ between the shedding groups. Cryptococcal genotypes were equally distributed across shedding groups. Conclusions. Discordancy between CrAg shedding and expected shedding based on quantitative fungal burden is associated with detectable immunologic differences in CSF, primarily among secreted cytokines and chemokines produced by antigen-presenting cells and Th2.

Cryptococcal meningitis is the most common cause of adult meningitis in Africa and accounts for 20% of acquired immune deficiency syndrome (AIDS)-associated mortality in sub-Saharan Africa [1–4]. With amphotericin-based combination antifungal therapy, 10-week mortality from human immunodeficiency virus (HIV)-associated cryptococcosis can be as low as 20%–30% [5–7]. However, at the end of amphotericin treatment, 40%–50% of individuals continue to have viable Cryptococcus neoformans in their cerebrospinal fluid (CSF), which has historically been associated with 2- to 3-fold excess risk of detrimental clinical outcomes, including, death, immune reconstitution inflammatory syndrome (IRIS), or relapse [8–12]. After amphotericin induction therapy, consolidation therapy of fluconazole 400 mg/day is recommended to further suppress infection and support long-term recovery [13, 14]. However, 400 mg/day fluconazole is primarily fungistatic, which may allow persistence of the fungus through consolidation therapy [15]. Persistent culture positivity and failure to clear the organism is thought to be detrimental in HIV, setting the stage for paradoxical IRIS upon ART initiation and ultimately increasing the risk of neurologic deterioration and death [16–18]. However low-grade culture positivity might not be detrimental if fungicidal therapy is continued and sterilizes the CSF as the immune responses are restored with ART. Few contemporary studies have investigated the detriments of residual cryptococcal infection after induction therapy. One recent study of 106 South Africans reported that residual fungemia was associated with a 3-fold higher hazard of paradoxical IRIS and an 8-fold higher hazard of culture-positive cryptococcal relapse when using traditionally recommended fluconazole 400 mg/day consolidation therapy [18]. During a recent clinical trial, we evaluated the association between persistent CSF culture positivity and detrimental clinical outcomes among participants treated with fluconazole 800 mg/day “enhanced consolidation” therapy.

Standard electrolyte monitoring and supplementation as compared to sporadic electrolyte monitoring and replacement improves mortality., Background Amphotericin B is the preferred treatment for cryptococcal meningitis, but it has cumulative severe side effects, including nephrotoxicity, hypokalemia, and hypomagnesemia. Amphotericin-induced severe hypokalemia may predispose the patient to cardiac arrhythmias and death, and there is very little data available regarding these toxicities in resource-limited settings. We hypothesized that standardized electrolyte management during amphotericin therapy is essential to minimize toxicity and optimize survival in sub-Saharan Africa. Methods Human immunodeficiency virus-infected, antiretroviral therapy naive adults with cryptococcal meningitis were prospectively enrolled at Mulago Hospital in Kampala, Uganda in 3 sequential cohorts with amphotericin B deoxycholate induction treatment. Intravenous fluid use was intermittent in 2001–2002, and universal in 2006–2012. In 2001–2009, serum potassium (K+) was monitored on days 1, 7, and 14 of treatment with replacement (K+, Mg2+) per clinician discretion. In 2011–2012, K+ was measured on days 1, 5, and approximately every 48 hours thereafter with universal electrolyte (K+, Mg2+) supplementation and standardized replacement. Clinical outcomes were retrospectively compared between fluid and electrolyte management strategies. Results With limited intravenous fluids, the 14-day survival was 49% in 2001–2002. With universal intravenous fluids, the 30-day survival improved to 62% in 2006–2010 (P = .003). In 2011–2012, with universal supplementation of fluids and electrolytes, 30-day cumulative survival improved to 78% (P = .021 vs 2006–2010 cohort). The cumulative incidence of severe hypokalemia (