bluuebunny/crossref_metadata_2025 huggingface dataset:
P-446. Outcomes of Hospitalization due to Cryptococcal Meningitis in a High-Resource Setting, 2015-2022
Authors: Fetters Kirk B , Ziegenbein James C , Chow Erica , Hatlen Timothy
Published: January 2025

Background

There is a paucity of outcome data in high-resource settings for cryptococcal meningitis (CM) in persons living with HIV (PWH). Novel induction regimens, such as the first-line recommended regimen from the World Health Organization, may reduce the duration of hospitalization and drug-associated adverse events with similar treatment outcomes. However, these regimens were not compared to the standard of care used in high-resource countries, leading to a reluctance to change current practice. Randomized controlled trials to compare these strategies would be cost-prohibitive in high-resource settings. To work towards quality observational data on this subject, we sought to describe medication-related adverse effects (AE) and mortality of PWH hospitalized with CM at our institution.Table 1:Patient Characteristics

Methods

We retrospectively obtained all electronic medical records associated with inpatient encounters and an HIV diagnosis occurring between 2015-2022 at Harbor-UCLA Medical Center in Los Angeles County, California. We screened for discharge diagnoses of CM or the immune reconstitution inflammatory syndrome due to CM (CM-IRIS). We abstracted demographic, diagnostic, therapeutic, and outcome data from these patient records.Table 2:Diagnostics and Patient Outcomes

Results

Thirty-one PWH were hospitalized with CM and/or CM-IRIS for a total of 51 admissions. Of these, 26 (83.9%) were cisgender men, 3 (9.7%) were cisgender women, and 2 (6.5%) were transgender women. The median age was 36 years old (IQR 30-46), and 21 (67.7%) were of self-identified Hispanic ethnicity. The median time since diagnosis of HIV was < 1 year (IQR 0-5.5). All patients were prescribed liposomal amphotericin B at 3-4mg/kg/day and flucytosine (5-FU) 100mg/kg/day for initial treatment. Fifteen (48.4%) patients failed to complete the 2-week induction, 10 (32.3%) due to AE. In-hospital mortality occurred in 4 (12.9%) patients, and 1-year mortality was documented for 7 patients (22.6%). Five patients (16.1%) had unknown status at 1 year.

Conclusion

We report a 1-year mortality of 22% in PWH hospitalized for CM in a high-resource setting compared to about 30-40% reported globally. However, 48% of patients were unable to complete induction, 32% due to adverse drug effects, emphasizing the importance of investigating the effectiveness of novel approaches to therapy.

Disclosures

All Authors: No reported disclosures
P-447. Anal Pap Smear Trends in Patients Living with HIV and History of Malignancy in a Single-Center Retrospective Observational Study
Authors: Rybolt Lauren E , Velez Ana , Shah Shivan , Pasikhova Yanina , Pardo Shylah Moore , Coghill Anna , Islam Jessica , Greene John
Published: January 2025

Background

The elevated rates of squamous cell carcinoma of the anus (SCCA) in persons living with HIV (PLWH) have led to greater awareness for screening with anal Pap cytology. While there is a premise that higher states of immunosuppression carry a greater risk of developing SCCA, no current studies describe this in the setting of PLWH with a history of solid or hematologic malignancy. The objective of this study is to review outcomes of anal Pap screenings in PLWH and a history of either solid or hematologic malignancies. With this study, we aim to outline potential risk factors associated with anal dysplasia in PLWH and a history of cancer.

Methods

This single-center retrospective cohort study included patients ≥ 18 years of age with a history of solid or hematologic malignancy who were followed at a cancer center clinic for HIV care between 2020-2024 and underwent anal Pap screening during this period. Demographics, pathology results, and clinical characteristics were obtained by chart review.

Results

The study identified 12 patients to date, with a mean age of 51 and male-to-female ratio of 5:1. Abnormal cytology on anal Pap was present in 83.3% (n=10) of patients with 50% (n=5) of these abnormal screenings resulting in either high-grade squamous intraepithelial lesion (HSIL) or atypical squamous cells, cannot rule out high-grade squamous intraepithelial lesion (ASC-H). Most with abnormal cytology on anal Pap underwent high-resolution anoscopy (HRA) (n=7/10). High-grade cytology was present on biopsy in 57.1% of patients (n=4/7). Invasive SCCA was found during HRA in 1 patient who had ASC-H on anal Pap screening. Table 1 outlines demographic information and clinical characteristics. Figure 1 demonstrates cytology results.

Conclusion

Over 75% screened had abnormal cytology, emphasizing the high incidence of anal dysplasia in this set of PLWH and a history of malignancy. The percentages of abnormal cytology in this population with a history of malignancy appeared to be higher than in other studies, implying chronic ongoing immune activation, although future work to expand the cohort is needed for robust estimation. These results should prompt further investigation to understand the potential interplay of HIV and malignancy history on the risk for developing anal dysplasia.

Disclosures

All Authors: No reported disclosures
P-452. Factors Associated with Liver Fibrosis Development in HIV-Monoinfected Patients Within the Modern ART Era
Authors: Endreson Morgan L , Hsieh Hsing-Chuan , Joya Christie , Colombo Rhonda E , Schofield Christina , Lalani Tahaniyat , Larson Derek , Yabes Joseph , O’Connell Robert , Blaylock Jason , Agan Brian , Ganesan Anuradha
Published: January 2025

Background

Liver fibrosis (LF) is a significant contributor to morbidity and mortality in people living with HIV (PLWH). Using data from the US Military HIV Natural History Study (NHS), we examined prevalence and risk factors of LF in the era of fixed dose combination antiretroviral therapy (ART).Table 1.Pertinent Participant Characteristics Categorized by the Presence or Absence of Liver Fibrosis:

Methods

The NHS is comprised of military beneficiaries with HIV, who are often diagnosed and treated early due to mandatory screening and guideline-based initiation of ART. We included ART-treated NHS participants, diagnosed after 2006, without active hepatitis B or C infection. LF was defined as a FIB-4 Index >2.67, a validated, non-proprietary, readily available marker of LF based on age, platelets, and liver-associated enzymes. Risk factors examined included demographic, HIV-specific, and other recognized associations with LF, see Table 1 footnote for details. Participants characteristics were analyzed with either the Kruskal Wallis or Chi2 test. Cox proportional hazard models, adjusted for baseline and time-updated variables, were used to assess risk factors for developing LF.Table 2.Unadjusted and adjusted HR on liver fibrosis

Results

Among 1209 participants, followed for a median of 5.4 years, 60 (5.0%) met the criteria for LF. Overall, the median time to ART initiation was 2.4 months. The median time to LF was 2.5 years. At LF diagnosis the median age, CD4 count and viral load were 36 years, 526 cells/uL and 20 copies/mL respectively. Those with LF were older, had lower CD4 count and high VL at HIV diagnosis and more likely to initiate NNRTI based ART, table 1. In an adjusted model, LF was associated with female gender, hypertension, obesity, at risk drinking, and higher VL, while African American race, integrase strand transfer inhibitor (INSTI) use, and higher CD4 counts were protective, table 2.

Conclusion

In the contemporary ART era, in this young and promptly treated cohort, the prevalence of LF was 5%, suggesting liver-related morbidity remains an important concern. Our results underscore the protective effect of immune preservation (by timely initiation and continuation of ART) against LF; however, the observed protective association with INSTI-based regimens will need further study to determine long-term benefit. As observed previously, hypertension, at risk drinking, and obesity are modifiable risk factors that should be addressed.

Disclosures

All Authors: No reported disclosures
P-579. Putting our Heads Together: Multidisciplinary Approach to Persons Living with HIV with Unsuppressed Viral Load
Authors: Rothman Ryan , Oehler Cassandra , Bchech George , Moore Jasmine , hsiao Chiu-bin
Published: January 2025

Background

Advances in antiretroviral therapy such as the use of single tablet regimens, improvements in tolerability, medications with low resistance, and availability of long-acting injectable antiretroviral regimens have made HIV viral control an achievable goal for persons living with HIV (PWHIV), leading to a longer healthy life and significantly reduced risk of HIV transmission. However, there is a subset of patients (5-10% of PWHIV prescribed antiretroviral therapy) who have a persistently elevated viral load. We aimed to target these individuals for better HIV viral control.Figure 1:Barriers to HIV VL controlThe most common barriers encountered among the 38 patients discussed

Methods

We identified patients from 2019 to 2024 in our Ryan White funded clinic with uncontrolled HIV, defined as a viral load (VL) greater than 200 copies/mL. Patients were placed in three categories: high risk (persistent VL > 200), vulnerable (inconsistent VL < 200), or stable (consistent VL < 200 for less than 2 years). We held weekly multidisciplinary meetings to discuss high risk and vulnerable patients and form an individualized plan of action. This plan was then discussed and enacted for each patient.Figure 2:Interventions geared to overcome the barriersThe most common interventions used among the 38 patients discussed to help overcome their unique barriers

Results

73 patients were identified who fit into one of the three categories, including 39 high risk, 15 vulnerable, and 19 stable. Thus far, weekly meetings have been held for 38 of them. Figure 1 portrays the most common barriers to VL control, with many patients having multiple barriers. Each patient’s barriers were then addressed, with the most common interventions illustrated in Figure 2. Thus far, 11 patients have moved from the high risk group to the stable group, and 3 patients have moved from the vulnerable group to the stable group. VL trend from these 14 patients are shown in Figure 3.Figure 3:Viral load over time for 14 patients with improved HIV viral controlLogarithmic graph of the viral loads over time for 14 patients who have moved from high risk or vulnerable to stable

Conclusion

By identifying patients who were unable to bring their HIV VL under control and holding weekly multidisciplinary meetings to discuss specific barriers, we have been able to bring many high risk patients down to VL < 200. The most common barriers were related to mental health, substance use, and difficulty adhering to daily medications. The most common interventions were offering long-acting injectable regimens, increasing clinic visit frequency, and offering mental health support. We believe this multidisciplinary approach shows promise in decreasing the prevalence of unsuppressed HIV in clinical practice.

Disclosures

Chiu-bin hsiao, MD, Viiv, Gilead: Grant/Research Support
P-586. Weight Gain in Treatment Naïve Patients with HIV Prescribed with Integrase Strand Transfer Inhibitor (INSTI)
Authors: Ludden Thomas , Thomas Jeremy , Vaught Brianne , Meardon Douglas
Published: January 2025

Background

Advances in care for patients with human-immunodeficiency virus (HIV) have progressed significantly over the past few decades. Integrase strand transfer inhibitors (INSTI) are recommended as initial therapy for HIV treatment-naive patients due to virologic efficacy, tolerability, toxicity profile, and ease of dosing. Current guidelines suggest consideration of weight gain as a possible side effect. As with overall US population trends of increased incidence of obesity, this same trend is being seen in the rate of overweight/obese patients with a new diagnosis of HIV. In recent years, there has been increasing concern regarding weight gain specifically associated with antiretroviral therapy (ART). Prior studies have found that individuals who start or switch to a regimen containing certain integrase inhibitors or tenofovir alafenamide (TAF), especially in combination, are more likely to gain weight. Here we examine the treatment of naïve patients with INSTI by BMI classes (underweight/normal, overweight, and obese).

Methods

Baseline BMI and weight were collected for treatment naïve patients with HIV who were prescribed an INSTI. Patients taking medications considered to be beneficial for weight loss were excluded. Weight one year later (+/- 2 months) was collected and paired with the patient's baseline weight. Average weight change was summarized for all patients and patients in underweight/normal, overweight, and obese BMI categories.

Results

Overall, 220 patients who were prescribed INSTI began with an average weight of 83.9 kgs at baseline and increased to 86.8 kgs 1 year later with an average of 2.93 kgs ([95%] CI 1.385 – 4.484), P< 0.001). For the 86 patients with underweight/normal BMI, weight increased by 3.12 kgs ([95%] CI 1.754 – 4.484), P< 0.001). For the 72 patients with overweight BMI, weight increased by 2.30 kgs ([95%] CI 0.076 – 4.515), P=0.043). For the 62 patients with baseline BMI classified as obese, weight increased by 3.42 kgs ([95%] CI -1.17 – 8.016), P=0.141).

Conclusion

Treatment naïve patients with HIV prescribed with INSTI have statistically significant weight gain. These increases were also significant for patients with normal and overweight BMI at baseline but not for patients with a BMI classified as obese.

Disclosures

All Authors: No reported disclosures
P-608. Clinical Profile of GSK's Pentavalent Meningococcal ABCWY Vaccine: An Overview
Authors: Toneatto Daniela , Lattanzi Maria , Ypma Ellen , O’Brien Karen , Rubin Steven , Tomasi Cont Laura , Pedotti Paola , Sohn Woo-Yun
Published: January 2025

Background

GSK’s MenABCWY vaccine was developed to provide broad protection against invasive meningococcal disease by combining the antigenic components of the licensed 4-component meningococcal serogroup B vaccine (MenB-4C) and serogroups A,C,W,Y vaccine (MenACWY-CRM).

Methods

An overview of the MenABCWY vaccine’s profile was derived from its clinical development program of 12 controlled studies,1-10 which enrolled over 7000 adolescents and adults in 13 countries.

Results

For serogroup B (MenB), non-inferiority of MenABCWY (2 doses, 6 months apart) to MenB-4C (2 doses, 2 months apart) was demonstrated in a phase 3 study9 in terms of vaccine-induced bactericidal immune responses measured by endogenous complement human serum bactericidal antibody (enc-hSBA) assay. The enc-hSBA assay uses each vaccinee’s serum as source of complement and tests a panel of 110 MenB strains representing 95% of disease-causing isolates in the US and ∼89% of global circulating strains,11 and is thereby used to assess immunological vaccine effectiveness (iVE) in clinical studies, in conditions close to real-world settings. MenABCWY iVE was 78% (95% CI: 77–79) against the panel of 110 MenB strains; serum from 84% of participants killed ≥ 70% of strains.9 For serogroups A,C,W,Y, non-inferiority of MenABCWY (2 doses, 6 months apart) to MenACWY-CRM (1 dose) was demonstrated in phase 3 studies in MenACWY-primed10 and -naïve9 participants, with robust immune responses against each serogroup.9,10 Phase 2 data for all 5 serogroups show 2-year and 4-year antibody persistence5,8 and anamnestic booster responses2,5,8 at 2 years after primary MenABCWY vaccination, and similar immune responses with MenABCWY 0-6 and 0-11 months schedules.8 In phase 3, 1 MenABCWY dose was non-inferior to 1 MenACWY-CRM dose as booster in participants primed with MenACWY ≥ 4 years previously.10 The safety and reactogenicity profile of MenABCWY was favorable overall and consistent with that of MenB-4C.1-3,8,9

Conclusion

GSK’s combined MenABCWY vaccine is immunogenic, with demonstrated non-inferiority to MenB-4C and MenACWY-CRM vaccines, and a safety profile similar to that of MenB-4C.

FUNDING: GSK

Disclosures

Daniela Toneatto, MD, GSK: Employee|GSK: Stocks/Bonds (Public Company) Maria Lattanzi, MD, PhD, GSK: Employee|GSK: Stocks/Bonds (Private Company) Ellen Ypma, Msc, GSK: Employee Karen O’Brien, PhD, GSK: Employee Steven Rubin, PhD, GSK: Employee Laura Tomasi Cont, PhD, GSK: Employee|GSK: Stocks/Bonds (Private Company) Paola Pedotti, PhD, GSK: Employee|GSK: Stocks/Bonds (Private Company) Woo-Yun Sohn, MD, GSK: Employed by GSK|GSK: Stocks/Bonds (Private Company)
P-615. Knowledge, attitudes and practice towards routine vaccination among medical students, Kazakhstan, 2023
Authors: Balmagambetov Arystan , Zhuman Balaussa , Horth Roberta , Nabirova Dilyara
Published: January 2025

Background

In Kazakhstan, coverage for childhood immunizations has decreased in recent years. Healthcare workers have the ability to increase vaccine coverage if they are sufficiently trained and have correct knowledge, attitudes and practices (KAP) related to routine immunizations. To assess whether interventions are needed in pre-service medical training, we needed to understand current vaccine KAP in medical students.Table 1.Participant characteristics

Methods

We conducted a cross-sectional study among senior medical students in 3 universities in Karaganda, Astana and Almaty, from March to May 2023. We used multivariable logistic regression to test association with adequate knowledge, attitudes, and practices (KAP); threshold for adequate scores for questions in each domain was 70%. Adjusted odds ratios (OR) and 95% confidence intervals (CI) are reported.Figure 1.Factors associated with vaccine practice among medical students in Kazakhstan

Results

We interviewed 3,956 students: 1,716 (43%) in Astana, 1,313 (33%) in Almaty, and 927 (24%) in Karaganda. Of these, 74% were female, and 65% were 21-23 years old. Additionally, 89% were studying general medicine, 8% pediatrics, and 3% public health. Fewer than half (38%) reported having received training on vaccination. Adequate KAP scores were 11% for knowledge, 55% for attitudes, and 17% for practices. Most (74%) believed common myths about routine vaccinations, including 62% believing that the flu vaccine causes flu. Knowledge scores < 70% were associated with attitude scores < 70% (OR: 1.72; CI=1.37–2.17) and practice scores < 70% (OR: 1.66; CI=1.30–2.11). Attitude scores < 70% were associated with being male vs female (OR: 1.25; CI=1.07–1.47), living with anyone < 18 years old vs not (OR: 1.37; CI=1.08–1.73), and living in Astana vs Karaganda (OR: 1.69 CI=1.41–2.03). Practice scores < 70% were associated with living with anyone >65 years old vs not (OR: 1.32; CI=1.03–1.72), Islam religion vs no religion (OR: 2.03; CI=1.65–2.50) and having attitude score < 70% vs ≥70% (OR: 2.99; CI=2.45–3.66).

Conclusion

Our study revealed markedly low levels of correct KAP related to routine immunizations. These results demonstrate the need to increase training on vaccination among medical students, especially among pediatric and general medicine students who will be involved in immunizations. Trainings should address common myths about routine immunizations.

Disclosures

All Authors: No reported disclosures
P-616. Sociodemographic and Clinical Factors Affecting Vaccination after Pediatric Solid Organ Transplantation at Duke University
Authors: Blatt Adam , Chang Yeh-Chung , Wang Yunfei , Heston Sarah M
Published: January 2025

Background

Pediatric solid organ transplant (SOT) recipients are at increased risk for vaccine preventable illnesses (VPI). They frequently receive vaccines after transplantation when immunosuppressive medications and cytopenias may impact their immune response to routine childhood vaccines. Current guidelines recommend monitoring vaccine-specific serologies to ensure optimal vaccine responses and to guide the need for repeat doses.

Methods

In this single-center retrospective cohort study, a multivariate logistic regression model was used to determine the sociodemographic and clinical factors associated with delays in starting post-transplant vaccines and adherence to post-vaccine serologic monitoring among 199 pediatric patients who received a SOT at Duke University between 2014-2023. The prevalence of cytopenias at the time of post-transplant vaccination was also described.

Results

Out of 150 children eligible for post-transplant vaccines (Table1), 48 (32%) failed to start catch-up vaccines within 2 years of transplantation. Older children (OR=0.877, 0.83-0.927) and children with private insurance (OR=0.458, 0.211-0.993) had significantly decreased odds of early catch-up vaccines (Table 2). Hepatitis B serologies were obtained in 23% of patients after post-transplant vaccination, but titers against the remaining non-live childhood vaccines were only obtained in 1-8% of children (Table 3). Approximately 53% of all children had neutropenia or lymphopenia (less than 1500 x 10^6 cells/L) at the time of post-transplant vaccination, with heart and intestinal/multi-visceral transplant recipients having the highest rates at ∼75% (Table 4).

Conclusion

These findings identify pediatric SOT recipients most at risk for delayed post-transplant vaccines. The associations between vaccine delay and private insurance and older age warrant further investigation. The extremely low rates of vaccine-specific serologic monitoring and the high prevalence of cytopenias at the time of vaccination raise concerns that pediatric SOT recipients are insufficiently protected from VPI. Future work will determine the impact of cytopenias on vaccine response and will address inequities in vaccination among pediatric SOT recipients.

Disclosures

All Authors: No reported disclosures
P-618. Investigating the Relationship Between COVID-19 Vaccine Accessibility and Coverage in Seattle and King County
Authors: Bemanian Amin , Mosser Jonathan F
Published: January 2025

Background

The COVID-19 pandemic presented unique challenges for public health and healthcare organizations delivering novel vaccines. For pediatric patients, it was further complicated by a rolling timeline for authorization and differences in products based on the patient’s age. Previous research has shown that spatial accessibility can affect health service utilization. There has been limited literature regarding COVID-19 vaccine accessibility, especially in pediatrics. For this project, we calculated the spatial accessibility of the pediatric COVID-19 vaccine in King County, WA, USA and then investigated the relationship between COVID-19 vaccine accessibility with rates of vaccine uptake/coverage.

Methods

The study was a cross-sectional ecological analysis with data from July 2022. Publicly available data was used to identify locations of vaccine sites in King County, WA and find ZIP code tabulation area (ZCTA) level vaccination coverage rates. Spatial accessibility was calculated using an enhanced two step floating catchment area (E2SFCA) technique. Spatial regression analyses were done to measure the relationship between vaccine accessibility, coverage, and other socioeconomic and demographic variables.

Results

Higher rates of vaccine accessibility and vaccine coverage were found in adolescents (12-17-year-old) relative to school age children (5 to 11-year-old). Vaccine accessibility scores were higher in ZCTAs with higher rates of adult educational attainment. Vaccine accessibility was positively associated with coverage in the univariable analysis, and this relationship was found to be modified by ZCTA educational attainment in the multivariable models and stratified analysis.

Conclusion

This study demonstrates how COVID-19 vaccine accessibility can be calculated in a region. Additionally, this study showed the relationship between vaccine accessibility and coverage was affected by educational attainment and other socioeconomic factors. These findings may be helpful in planning distribution of future vaccines.

Disclosures

All Authors: No reported disclosures
P-700. Examining the Knowledge, Availability, Access and Uptake of RSV Immunoprophylasis among RSV Hospitalized Infants
Authors: Shelley Jamee T , Walsh Tyler , Gorham Lisa , Madrian Erika , Neiditz Hannah , Torres Ana V , Prater Jasmine , Heroux Megan D , Catherall David , Sun Brian , Agha Humza , Ott meghan , True Kelly , Barganier Lori B , Cindy Terrill M , Reich Patrick J , Newland Jason G
Published: January 2025

Background

Every year, up to 80,000 children less than 5 years are hospitalized due to RSV infection and those less than 1 are at greatest risk for ICU admission. In the Fall of 2023, 2 immunoprophylaxis strategies, nirsevimab for infants and Abrysvo for pregnant women, were approved to prevent serious RSV infection in infants. This study investigates whether caregivers of infants admitted with RSV were aware, had access of RSV and whether the RSV vaccine was received.Table 1:RSV Respondents Demographics

Methods

A survey study was conducted among families with infants born between April 2023 and March 2024, who were admitted to St. Louis Children's Hospital and tested positive for RSV. The survey asked questions among caregivers regarding the main themes: awareness, availability and uptake of the immunoprophylaxis.Table 2:RSV-related Caregiver Responses

Results

A total of 34 surveys were completed with 3 moms having received Abrysvo and 6 infants having received nirsevimab. The demographics of the respondents were 12% Black, 74% White, and 9% Multiple races; and 6% Hispanic (Table 1). Of those receiving immunoprophylaxis, 5 and 4 had public and private insurance, respectively (Figure 1). Of the 97% of mothers that received regular prenatal care, only 9% received Abrysvo (Table 2). Of the 31 mom not receiving Abrysvo, 16% responded that the RSV vaccine was not available and 48% responded that the vaccine was not offered (Table 2). Of those infants with RSV who had not received nirsevimab, 65% were not offered the immunization, nirsevimab and Beyfortus. Of those not offered nirsevimab, 32% reported it was not available, 18% did not know about it, and 2% of moms received Abrysvo (Table 2).Figure 1:Mom or Infant Receiving Immunoprophylaxis by Insurance Status

Conclusion

For those moms and infants not receiving Abrysvo or nirsevimab, awareness and availability were important reason. In the upcoming RSV season, more efforts are needed to ensure these factors are addressed in delivering these important immunoprophylaxis products.

Disclosures

Jason G. Newland, MD, MEd, Moderna: Grant/Research Support|Pfizer: Grant/Research Support
P-707. Relative Effectiveness of Cell-Based Influenza Vaccines versus Egg-Based Influenza Vaccines: A Review of Test-Confirmed and Clinical Diagnosis-Based Outcomes
Authors: Imran Mahrukh , Mifsud Edin , Haag Mendel , McGovern Ian
Published: January 2025

Background

Cell-based influenza vaccine viruses may more closely match recommended vaccine strains than egg-based options. A previous systematic literature review (SLR) and meta-analysis evaluated the relative effectiveness (rVE) of cell-based quadrivalent influenza vaccine (QIVc) versus standard-dose, egg-based quadrivalent or trivalent influenza vaccines (QIVe/TIVe) in preventing either clinically diagnosed or test-confirmed influenza. We sought to build on that prior evidence and evaluate the rVE of QIVc versus QIVe/TIVe by separately analyzing test-confirmed and clinically diagnosed influenza.

Methods

Studies reporting on the rVE of QIVc vs QIVe/TIVe among persons aged 4–64 years were identified from a prior SLR (PROSPERO CRD42020160851) that included studies published between 01-January-2016 and 25-February-2022. Additionally, a scoping review was conducted to identify additional studies published between 25-February-2022 and 01-March-2024. A DerSimonian and Laird random effects model was applied for the meta-analyses.

Results

The SLR included 10 relevant publications (n=3 test-confirmed; n=7 clinical diagnosis) spanning three influenza seasons from 2017–2020. An additional test-confirmed study covering the 2017–2020 influenza seasons was identified from the scoping review. Among persons aged 4–64 years, the pooled rVE demonstrated a consistent benefit of QIVc for both outcome types, with estimates of 11.9% (95% CI, 3.0%–20%; n studies=3) for 2017–2018, 11.8% (4.2%–19.4%; n=2) for 2018–2019, and 10.0% (2.7%–16.7%; n=1) for 2019–2020 in preventing test-confirmed influenza and 18.7% (8.7%–27.6%; n=2) for 2017–2018, 5.9% (4.3%–7.5%; n=2) for 2018–2019, and 10.1% (6.1%–14.0%; n=2) for 2019–2020 in preventing clinically diagnosed influenza.

Conclusion

For persons aged 4–64 years, QIVc was consistently more effective than QIVe/TIVe over the three influenza seasons for both test-confirmed influenza and clinically diagnosed influenza. The results do not suggest systematic over or underestimation of rVE for prevention of clinically diagnosed compared to test-confirmed influenza.

Disclosures

Mahrukh Imran, MScPH, CSL Seqirus: Employee Edin Mifsud, PhD, CSL Seqirus: Employee|CSL Seqirus: Stocks/Bonds (Private Company) Mendel Haag, PhD, PharmD, CSL Seqirus: Employment|CSL Seqirus: Stocks/Bonds (Public Company) Ian McGovern, MPH, CSL Seqirus: Employee|CSL Seqirus: Stocks/Bonds (Public Company)
P-767. Unveiling Tuberculosis: A Perspective on Active vs. Subclinical Pulmonary Tuberculosis
Authors: Cardenas-Maldonado Diana D D , Chevalier Thomas , Herc Erica , Lanfranco Odaliz Abreu , Suleyman Geehan
Published: January 2025

Background

Despite being preventable and curable, tuberculosis (TB) remains one of the world’s leading infectious disease killers with 1.5 million people dying each year worldwide. The U.S. has one of the world’s lowest rates of TB; however, cases increased 16% from 2022 to 2023. Although risk factors and outcomes associated with TB have been described, reports characterizing TB disease in the U.S. are limited.

IQR: interquartile; USA: United States of America; BMI: Body Mass Index; HIV: human immunodeficiency virus; TNF-alpha inhibitors: Tumor necrosis factor-alpha inhibitors; TB: tuberculosis.

Methods

Retrospective case series of patients with TB disease at Henry Ford Health in Southeast Michigan from Jan 2019-Dec 2023. Demographics, risk factors, clinical manifestations, treatment, and outcomes were evaluated.  Active and subclinical TB were compared. Active TB was defined as positive imaging and/or microbiologic assay with clinical TB-related symptoms, and subclinical TB as positive imaging and/or microbiologic assay without symptoms.

AFB: Acid-Fast-Bacilli; MTB: Mycobacterium tuberculosis; PCR: polymerase chain reaction; IQR: interquartile; TB: tuberculosis; RIPE: Rifampin, Isoniazid, Pyrazinamide, Ethambutol; INH: Isoniazid; RIF: Rifampin.

Results

53 patients were included, of whom 18 (33%) were black and 34 (64%) were male with a median age of 55 years (Table 1). Almost half were born in the U.S., and a quarter lived in Detroit. Prior TB exposure (30%), international travel (21%), persons who inject drugs (23%), and incarceration (17%) were common risk factors. 47 (89%) patients had active TB, and cough (68%) was prevalent. Consolidation and nodular patterns were frequently seen on imaging; cavitation occurred in 42% of cases. All had sputum smear microscopy and culture ordered; MTB PCR was obtained in 72% of cases (Table 2). Both were more likely to be positive in those with active TB. Most patients required inpatient admission; median time to airborne isolation precautions was longer in the subclinical group. Length of stay was prolonged in both groups. All patients with active TB received treatment, whereas 83% were treated in the subclinical group. Most were treated for at least 6 months. Among those completing treatment, 68% achieved cure and 15% expired.  

Conclusion

In this large cohort of TB patients, almost half were US-born and a third had a known TB exposure. Although less common, subclinical TB contributed to 11% of cases. Despite treatment, clinical cure was suboptimal with a 15% mortality. Early recognition and treatment of latent and active TB are critical disease control and prevention strategies.

Disclosures

All Authors: No reported disclosures
P-787. Potential Impact of Repeating Unexpected Positive Interferon Gamma Release Assays
Authors: Kiritsy Michael , Turner Nicholas A , Zavala Sofia , Stout Jason E
Published: January 2025

Background

Interferon gamma release assays (IGRAs) are more specific for tuberculosis infection than the tuberculin skin test but also have higher test-retest variability. False positive tests may occur in low prevalence populations. As such, repeating unexpected positive tests (positive tests in patients without exposure risk) is recommended.Table:Initial and repeat IGRA results

Methods

We performed a retrospective electronic record review of all patients for whom a QuantiFERON (IGRA) was performed in Duke University Health System between 10/1/2014-5/3/2024. We examined patterns of repeat testing and ascertained the potential clinical impact of repeat testing.

Results

In total, 59,485 IGRAs were performed on 49,850 patients during the study period. 7,076 patients had repeat IGRA testing (median 2 IGRAs, range 2-9). Of these, 6137 had negative, 297 positive, and 642 indeterminate results on the first test. When repeat testing was performed, 743 (11%) patients had a different result on the second test (Table). Of patients with initial positive results, 104/297 (35%) had a negative result on the second test, which was performed a median of 110 days later (IQR 16-420 days). 86 patients had a negative first test but a positive second test; of these, 38 had a third test performed that was negative in 27 (71%) and positive in 11 (29%).

Conclusion

In a low-prevalence setting, repeating positive IGRA tests potentially avoided unnecessary preventive treatment in over a third of patients with an initial positive test and in two-thirds of patients with a prior negative test.

Disclosures

Nicholas A. Turner, MD, MHSc, PDI: Research contract|Purio Labs: Research contract
P-796. The Deadly Raise of NTM : An Observational Study on Clinical profile and Outcome Of NTM Disease
Authors: Teja Vasireddy , Saha Bibhuti , Haldar Soumendranath
Published: January 2025

Background

NTM is ubiquitously present in the environment. When these microorganisms shed, they produce biofilms that increase the likelihood of infection.

CLINICAL AND RADIOLOGICAL FEATURES OF NTM

Methods

STUDY PERIOD: 1 YEAR

STUDY DESIGN:

Cross-sectional observational study

STATISTICAL ANALYSIS:

Categorical variables will be expressed as %

NTM VARIOUS CLINICAL SITES

Results

25 cases were selected for analysis. Out of 25 (40% ) were port site infection and 12 % pulmonary. Most common symptom was discharge (60%) . Empirical antibiotics were started in 100% . ID referral was sent in all .RF were seen in 40%. Scans was showing sinus tract formation or deep seated abscess among (80%); . AFB stain was positive in 80% cases and CB-NAAT negative in 100% cases. Culture positivity in 56% , among 15 samples sent for PCR it was positive in 10 (66.6%); among 10 cases sent for sequencing 8(80%) cases were positive. Rapid growers 92% and then slow growers were seen in 8% cases. most common species was M.chelonae (28.5%) followed by M.fortuitum and abscessus (21.4%); among 3 species of abscessus sub species were able to identify in one case and it was boleti 33.3%. slow growers MAC and kansasi were identified 7% each. NTM culture was given positive but species identification was not done in 14.2% cases. Culture was negative in 44% of cases. DST was done in 14 cases and genotypic was able to do in 5 cases and erm gene detected (40%) cases. Phenotypic DST was done in all culture positive isolates(n=14), among them cotrimoxazole (92.8%); Amikacin and linezolid was sensitive in 85.7% isolates, imipenem,levofloxacin and tigecycline in 71.4% and macrolide was sensitive in 57.1% cases only. Various combination regimens were used and most common combination used were amikacin,levofloxacin,macrolide and amikacin,linezolid,levofloxacin and amikacin,levofloxacin,cotrimoxazole in 24% cases; and 1 case had treatment with amikacin,linezolid,tigecycline . 40 % cases used combination treatment for 1 year or longer;20 % cases only used 6 months of therapy. Side effects like GIT intolerance in 80% cases; renal toxicity was seen in 40% cases. Upon follow up death in 8%; resolution in 76% , culture negativity 71.4% non-resolving/recurrence 16%

Conclusion

Most of the patients with NTM are misdiagnosed and are treated as tuberculosis

ANTIBIOTIC SUSCEPTIBILITIES AMONG VARIOUS NTM ISOLATED

NTM IMAGE 4

Disclosures

All Authors: No reported disclosures
P-797. Household Contact Tuberculosis Screening Experience and Predictors of Tuberculosis Disease Diagnosis in Rural Tanzania
Authors: ILAIWY Ghassan , Lukumay Saning’o , Agustino Domitila , Mejan Paulo , Simeon Kusulla , Mduma Estomih , Heysell Scott , Thomas Tania
Published: January 2025

Background

One third of people with TB disease (PWTB) remain undiagnosed, experiencing prolonged illnesses before diagnosis. To close this gap, the World Health Organization and national guidelines recommend TB screening for all household contacts (HHCs) of index PWTB. HHC TB screening experiences vary between countries, and between rural and urban parts within the same country. Therefore, we aimed to characterize the HHC TB screening and explore predictors of TB disease diagnosis among HHCs in Rural Tanzania.

Methods

We used data from a prospectively enrolled cohort of index PWTB and their HHCs in Haydom, Tanzania. We describe the testing recommended as part of HHC TB screening and use a multivariate regression model to explore predictors of TB disease diagnosis.

Results

The cohort enrolled 120 index PWTB with 398 HHCs. 261 HHCs (66%) from 85 households completed TB screening with sputum and chest x-ray recommended for 121 (46%) and 3 (1%) HHCs respectively. 18 HHCs (4.5%) were diagnosed with TB disease, 14 of them with no sputum or CXR recommended. HHCs with TB symptoms and HHCs of index PWTB with pulmonary TB or HIV were more likely to be diagnosed with TB. Only 10 HHCs completed six-months of daily isoniazid TPT out of 61 HHCs who started TPT (16.3%) and 79 HHCs who were eligible (12.7%).

Conclusion

The recommended sputum and imaging studies to complete HHC TB screening and short TPT regimens have suboptimal penetration in this rural high-burden setting. Innovative testing and coverage modalities are needed to bridge the gap.

Disclosures

All Authors: No reported disclosures
P-798. Non-Tuberculosis Mycobacterial Infections at a National Cancer Institute-Designated Comprehensive Cancer Center in Florida
Authors: Pasikhova Yanina , Snyder Matthew , Morrison Austin , Handley Guy , Syed Misbahuddin , Cannella Anthony P
Published: January 2025

Background

Non-tuberculous mycobacteria (NTM) are environmental organisms which become opportunistic pathogens in certain patient populations. NTM prevalence has increased globally, thought to be due to the increased diagnostic testing and availability of population-based studies. This is especially true in Florida, where we have previously documented more cases of Mycobacterium abscessus group compared to M. avium Complex (MAC) group. Current literature of NTM infections in oncology patients is minimal and represents a unique area for study. Here we present our epidemiological and clinical presentation of NTM infection cases at a National Cancer Institute-designated comprehensive cancer center.Figure 1.Patient Characteristics

Methods

Retrospective, Institutional Review Board-approved, single-center cohort study, of adult patients with microbiologically proven NTM infections who presented from 2020 to 2023. Demographic, laboratory, and susceptibility data were retrieved from the electronic medical record system and evaluated to show institutional patterns.Figure 2.Microbiological Characteristics for Overall Population

Results

Ninety-three cases of NTM infection met assessment criteria. Baseline characteristics are shown in Figure 1. A large proportion were female (71%) and white (90%). Many had a past or active cancer (80%), with skin (23%), lung (22%), and breast (13%) most prevalent. MAC (52%) and M. abscessus group (31%) were the most common NTM isolates (Figure 2). The majority were pulmonary infections (81%), with the integument accounting for most non-pulmonary sites (78%). Positive cultures were most frequently obtained via bronchoalveolar lavage (62%) followed by sputum (13%). Figure 3 offers insight into infection/culture site and cancer type stratified by organism, while susceptibility patterns are summarized in Figure 4.Figure 3.Site of Infection/Culture and Type of Cancer Stratified by Organism

Conclusion

NTM infections at our institution were primarily caused by MAC or M. abscessus group and were typically pulmonary in nature, isolated via bronchoalveolar lavage. Most occurred in patients with a solid tumor malignancy. Further research is needed to delineate prevalence patterns, microbiological characteristics, and treatment approaches of NTM infections in our site’s population.

Susceptibility by Organism

Disclosures

All Authors: No reported disclosures
Neurocognitive Impairment Among Cryptococcal Meningitis Survivors in Uganda, a Prospective Cohort Study
Authors: Nsangi Laura , Hullsiek Kathy Huppler , Dai Biyue , Namudde Alice , Menya Grace , Ssebambulidde Kenneth , Tugume Lillian , Nuwagira Edwin , Rhein Joshua , Williams Darlisha A , Musubire Abdu K , Boulware David R , Meya David B , Abassi Mahsa
Published: January 2025

Background

Neurocognitive impairment in HIV-associated cryptococcal meningitis survivors remains poorly characterized. We sought to identify risk factors associated with sustained neurocognitive impairment.

Methods

Cryptococcal meningitis survivors from the ASTRO-CM trial underwent neurocognitive assessment at 12 weeks. A composite quantitative neurocognitive performance score (QNPZ-8) was calculated as a mean of 8 independent z-scores. Participants were classified by QNPZ-8 score as having mild (QNPZ-8 ≥−1), moderate (−2 < QNPZ-8 < –1), or severe (QNPZ-8 ≤−2) impairment compared with the reference cohort of HIV-negative Ugandan adults. We compared differences in baseline demographics and clinical and laboratory variables by impairment categories.

Results

One hundred fifty-two participants completed ≥5 of the 8 neuropsychological tests and were included in the analysis. Overall, 37% (57/152) exhibited mild (QNPZ-8 ≥−1), 37% (56/152) moderate (−2 < QNPZ-8 < –1), and 26% (39/152) severe impairment (QNPZ-8 ≤−2). The overall mean QNPZ-8 score (SD) of −1.4 (0.82) denoted moderate neurocognitive impairment at 12 weeks. At baseline, lower weight (P = .03), Glasgow Coma Scale score <15 (P = .03), and education ≤7 years (P < .001) were more frequently observed among those with severe neurocognitive impairment at 12 weeks. Education ≤7 years (odds ratio, 6.13; 95% CI, 2.96–12.68; P < .001) and Glasgow Coma Scale score <15 (odds ratio, 2.61; 95% CI, 1.23–5.57; P = .013) were associated with moderate or severe neurocognitive impairment.

Conclusions

Neurocognitive impairment is prevalent at 12 weeks post-treatment in HIV-associated cryptococcal meningitis. Education level and Glasgow Coma Scale score <15 are associated with worse neurocognitive performance. Our findings underscore the need to further evaluate the impact of cryptococcal meningitis on neurocognitive outcomes.
Promoting owners’ shared parking willingness considering management mechanisms in community network
Authors: Wei Qingqi , Xiao Guomei
Published: January 2025

Shared parking effectively optimizes urban parking resources while making full use of private parking spaces and satisfying the growing demand for parking in large cities. However, some owners are unwilling to share private parking spaces and oppose the community in conducting shared parking projects. To promote the sharing of private parking spaces, we use a complex network evolutionary game method to depict the impact of owners’ unfavorable relationships on individuals’ decision processes in real time and explore the impact of management mechanisms on owners’ willingness to share. The results demonstrate that experience-weighted attraction learning strategies that focus on experiential learning and adaptability are more conducive to promoting owner cooperation, whereas neighbor-avoidance conflict costs resulting from interactions between owners restrict cooperative behavior, and a higher number of network owners is detrimental to cooperation. A platform that improves the rejection rate of parking requests and overtime inconvenience cost is conducive to cooperation, but overtime probability and time window conflict cost reduce owners’ willingness to share. The government can lessen these adverse effects by adding compensation to all owners and increasing the public opinion adjustment coefficient to promote cooperative behavior and increase the number of shared parking spaces.
Chronic treatment of old mice with AICAR reverses age‐related changes in exercise performance and skeletal muscle gene expression
Authors: Wilcox Shalene H. , Calixto Jouber , Dray Steven D. , Rasch Daniel M. , Smith Andrew H. , Brodowski Kole D. , Hill Jonathon T. , Thomson David M.
Published: January 2025

Sarcopenia refers to the decline in muscle mass and function that occurs with advancing age. It is driven by alterations in multiple cellular processes. AMP‐activated protein kinase (AMPK) is a cellular energy sensor that opposes many age‐related changes, making it an attractive target for the treatment of sarcopenia. This study aimed to test the effect of chronic treatment of old mice with the AMPK‐activating prodrug, AICAR, on treadmill running capacity and muscle mass, force production, gene expression, and intracellular markers relevant to sarcopenia. Old (23 months) mice were tested for treadmill running capacity, then randomly assigned to receive daily treatment with AICAR (OA; 300 to 500 mg/kg, delivered via subcutaneous injection) or an equivalent volume of saline vehicle (OS) for 31 days. Young (5 months) saline‐treated mice (YS) served as controls. Treadmill posttesting was performed after 24 days, and the mice were euthanized after 31 days of treatment. Extensor digitorum longus (EDL) muscles were tested for force generation and RNA sequencing, RT‐PCR, and western blotting were performed on quadricep muscles. Treadmill running capacity declined from pre‐ to posttesting by 24.5% in OS mice. This decline was not observed in YS or OA mice. Quadricep weight was ~8% higher, and tetanic force production by the EDL muscle increased by 26.4% in OA versus OS. These phenotypic improvements with AICAR treatment were accompanied by changes in gene expression in OA/YS versus OS muscles consistent with the “rejuvenation” of gene ontologies associated with connective tissue, neurodegenerative disease, Akt signaling, and mitochondrial function, among others. AICAR increased the mitochondrial markers cytochrome C by ~33%, and citrate synthase by ~22%. Serum insulin‐like growth factor‐1 levels increased, and Akt phosphorylation tended (p = 0.07) to increase with AICAR treatment. Although protein levels of the mTORC1 signaling pathway intermediate, rpS6, were higher in OA versus OS muscles, the phosphorylation of mTORC1 pathway intermediates was unaffected. On the other hand, gene expression of the muscle‐specific ubiquitin ligases Mafbx and Murf1 were reduced with AICAR treatment. AICAR treatment mildly increased/preserved muscle mass and force production and prevented a decline in treadmill running performance in old mice. These effects were associated with altered skeletal muscle gene and protein expression, suggesting improved mitochondrial content and metabolic signaling (particularly through Akt) as contributing factors to the observed phenotypic effects. Our findings support further development of AMPK‐activating drugs as a therapeutic strategy for improving age‐related organismal dysfunction and sarcopenia.