Disseminated Disease Research Articles

Advances in the Pathogenesis, Diagnosis, Treatment, and Prognosis of Marginal Zone Lymphoma.

The management of marginal zone lymphoma (MZL), an indolent B-cell non-Hodgkin lymphoma, requires a personalized and adaptive approach due to its clinical and prognostic heterogeneity. We believe treatment should emphasize a balanced strategy considering the subtype, disease burden, symptoms, and actionable genetic or environmental factors, such as infections or autoimmune diseases. For asymptomatic patients with low tumor burden or disseminated disease, a watch-and-wait approach remains appropriate, given MZL's indolent nature and the risks of overtreatment. Conversely, for symptomatic or high-burden cases, early intervention with chemoimmunotherapy is recommended for effective disease control. Surgery remains essential for both diagnosis and the treatment of localized disease. Incorporating molecular profiling and prognostic models, such as MZL-IPI and POD24, is crucial for decision-making and risk stratification. Testing for infectious agents like Helicobacter pylori or Hepatitis C virus should be standard practice, as eradication therapy offers a targeted, less toxic, and effective option in select patients. With ongoing advancements in understanding dysregulated signaling pathways and the tumor microenvironment, we anticipate novel targeted therapies and combination regimens will further improve outcomes. We advocate for molecular testing at diagnosis to identify actionable biomarkers, particularly for patients with refractory or relapsed disease. Finally, MZL management requires vigilant follow-up with adjustments based on evolving disease features. Treatment decisions should integrate patient preferences, clinical context, and the latest evidence to maximize survival while preserving quality of life.

Comparison of mutational landscape in primary and metastatic pancreatic tumors.

781 Background: Genomic profiling has brought to the forefront the clinical relevance of intratumoral heterogeneity. Oncogenic KRAS mutation is the most common driver event in pancreatic ductal adenocarcinoma (PDAC), but little is known about how KRAS alteration may cooperate with other genetic lesions to support dissemination and growth of metastatic disease. Therefore, an improved understanding of molecular events affecting the clinical course of KRAS -altered PDAC is needed to identify biomarkers of early disease and expand the repertoire of targeted therapies. Methods: We retrospectively analyzed tissue samples from PDAC patients using the OncoExTra tumor-normal whole exome and whole transcriptome test between April 2018 and May 2024. The prevalence of actionable somatic alterations was determined overall and by specimen location (primary vs. metastatic). Fisher’s exact test with FDR-based correction for multiple testing was used to identify co-alterations with KRAS and 19 DNA damage response (DDR) gene alterations. Results: PDAC samples from 434 patients (51.2% female; mean age 65.4±10.9 years) were analyzed. KRAS alterations were detected in 369 (85.0%) samples: 198 (45.6%) primary and 239 (55.1%) metastatic. KRAS G12D (32.7%) and KRAS G12V (29.5%) were the most common KRAS mutations. The frequency of KRAS alterations was 85.9% and 84.5% in primary and metastatic samples, respectively. TP53 alterations occurred in 68.2% samples overall and in 64.6% and 71.1% of primary and metastatic samples, respectively. Examination of co-alterations in KRAS -altered versus KRAS -WT samples uncovered enrichment of TP53 alterations in KRAS -altered (277 samples, 75.1%) compared to KRAS -WT samples (19 samples, 29.2%) ( p <0.001). Also, BRAF mutations and SND1:BRAF fusions exclusively occurred in metastatic KRAS -WT samples, although the number of events was small ( n =4 and n =2, respectively). We also found that MTAP was significantly co-altered in metastatic KRAS -WT samples (n=6, 16.2%) compared to KRAS -altered samples (6 samples, 3.0%) ( p =0.004). A total of 21.9% of all PDAC samples had an alteration in at least 1 DDR gene. No associations were observed between KRAS alteration status and alteration in DDR genes. However, TP53 alterations were more frequent in non-DDR-altered samples ( p <0.001), while CDKN2B alterations were enriched in DDR-altered samples ( p =0.025). Conclusions: We observed expected rates of alterations in known PDAC driver genes and uncovered higher co-occurrence of KRAS and TP53 alteration in metastatic samples. Additionally, TP53 alterations were less frequent in DDR-altered samples. Our findings suggest that a number of therapy approaches including BRAF, WEE1, PARP, and KRAS inhibitors as well as epigenetic modulators, alone or in combination, could improve clinical outcomes in PDACs with specific mutational profiles.

P-1293. Healthcare Costs Associated with Lyme Disease in a US Insured Population

Abstract Background An estimated 476,000 people are diagnosed and treated for Lyme disease (LD) each year in the United States (US). LD manifests as localized (e.g., single erythema migrans (EM)) or disseminated disease (e.g., multiple EM, arthritis, cardiac, and neurologic conditions). Healthcare costs for LD patients by clinical manifestation are understudied. This work aimed to assess costs of LD by manifestation in an insured US population. Methods This retrospective study identified LD patients in the Optum Market Clarity Integrated Claims and Clinical dataset from January 2016 through December 2022 based on LD diagnosis codes (A69.xx). Outpatient LD patients had claims for relevant antibiotics within 30 days of diagnosis. Inpatient LD patients had LD as a primary or secondary diagnosis with a LD-associated condition as primary. Cases were classified as disseminated, localized, or undetermined based on diagnosis codes for LD and LD-associated conditions, inpatient vs. outpatient services, and antibiotic treatment. Healthcare costs were assessed for 1) LD-specific costs during individual LD episodes, 2) all-cause 6-month follow-up costs vs. baseline costs for LD patients, 3) all-cause 6-month follow-up costs for LD vs. controls (matched 3:1 to cases by hard matching and propensity score matching on demographic and clinical characteristics). Costs were standardized across payer types and CPI-adjusted to 2022. Results During 2016-2022, 70,531 LD cases (mean age 45 years, 51% female) were identified. Mean (standard deviation) LD-specific total medical costs were $2,227 ($15,790) per episode, with $695 ($7,348) and $6,833 ($27,983) for localized and disseminated cases, respectively (Figure 1). Compared with a 6-month baseline, mean all-cause total costs during 6-month follow-up were $3,304 greater for LD diagnosed patients overall, $1,381 greater for localized, and $10,130 greater for disseminated (Figure 2). Compared to controls, mean total all-cause 6-month follow-up costs were greater by $4,098 for LD overall, $819 for localized, and $12,978 for disseminated (Figure 3). Conclusion Patients diagnosed with LD incurred substantial costs, driven by disseminated disease. This poses a large economic burden to the healthcare system. Effective preventive measures are needed. Disclosures Rebecca M. Fee, MPH, Optum: Employee Holly Yu, MSPH, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) L. Hannah Gould, PhD, MS, MBA, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) Amanda R. Mercadante, PharmD, Pfizer, Inc.: Stocks/Bonds (Public Company) Brian T. Campfield, MD, Pfizer: Advisor/Consultant John Halperin, MD, Abbott: Stocks/Bonds (Public Company)|Abbvie: Stocks/Bonds (Public Company)|Johnson & Johnson: Stocks/Bonds (Public Company)|Merck: Stocks/Bonds (Public Company)|Pfizer: Advisor/Consultant Mary G. Johnson, PharmD, MSPH, UHG/Optum: Employee|UHG/Optum: Stocks/Bonds (Public Company) Benjamin Chastek, MS, Optum: Employee|Optum: Stocks/Bonds (Public Company)

P-1291. Racial disparities in Lyme disease among beneficiaries of US Medicaid and Medicare

Abstract Background Lyme disease (LD) is the most common vector-borne disease in the US. Manifestations range from a localized rash to neurologic, cardiac, and musculoskeletal conditions during disseminated stages. LD incidence is highest among White persons in the US, but evidence suggests that people from racial and ethnic minority groups experience more severe disease. Methods We used a claims-based algorithm (≥ 1 LD ICD-10 code and appropriate antibiotics within 30 days) to identify LD cases among Medicaid (age < 19 and ≥ 19 years) and Medicare fee-for-service (age < 65 [persons with disabilities] and ≥ 65 years old) beneficiaries living in 16 high incidence states ( > 10 cases/100,000 population for ≥ 3 years) during 2016-2021. We calculated prevalence ratios for disseminated disease and hospitalization by racial group using White persons as the reference. Results There were 62,055 LD cases identified among Medicaid beneficiaries and 90,882 among Medicare beneficiaries. In Medicaid, 85% of cases were in White persons, 6% in Hispanic, 4% in Black, 4% in Asian/Pacific Islander, and 1% in Native American persons. In Medicare, 96% of cases were in White persons, with 1% or less reported in other groups. Non-White persons were more likely to be hospitalized at diagnosis, diagnosed outside of primary care, diagnosed outside of the peak months for LD transmission, to be female, and to have disseminated disease (Table 1). Medicaid beneficiaries and Medicare beneficiaries ≥ 65 years old who identified as Black, Asian/Pacific Islander, or Hispanic had a higher likelihood of disseminated disease than White persons. Among Medicaid beneficiaries < 19 years old, those who identified as Black, Asian/Pacific Islander, or Hispanic had a higher likelihood of being hospitalized at diagnosis than those who identified as White. Black Medicaid beneficiaries ≥ 19 and Medicare beneficiaries < 65 also had a higher likelihood of hospitalization (Table 2). Conclusion These data illustrate disparities in LD by race and ethnicity and suggest possible disparities by other characteristics including sex and, given the high rates of disseminated disease in Medicare beneficiaries < 65 years old, disability. Equitable interventions are needed to reduce disparities in LD recognition and severity. Disclosures L. Hannah Gould, PhD, MS, MBA, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) Sarah J. Willis, PhD, MPH, Pfizer, Inc.: Employment|Pfizer, Inc.: Stocks/Bonds (Private Company) Christopher G. Prener, PhD, Pfizer, Inc.: Employee|Pfizer, Inc.: Stocks/Bonds (Public Company) Stephanie A. Duench, PhD, Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds (Public Company) Holly Yu, MSPH, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) Jennifer Moisi, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) James H. Stark, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company)

216. Effectiveness of JYNNEOS Vaccination in Preventing Lesion Dissemination Among Individuals with Confirmed Mpox Infection

Abstract Background Observational studies during the global mpox clade IIb outbreak associated with male-to-male sexual contact have demonstrated the JYNNEOS vaccine prevents diagnosed mpox disease. However, effects of vaccination on mpox clinical presentations remain uncertain. Data Flow Chart Flow chart characterizing the mpox cases in California’s eligibility for inclusion in the present analysis in relation to their genders, clinical presentations, and vaccination statuses. Methods Male cases with confirmed mpox infection reported to the California Department of Public Health between May 12, 2022 and December 31, 2023 were interviewed about anatomical lesion sites. We ascertained cases’ vaccination statuses via linkage to the California Immunization Registry. We estimated JYNNEOS vaccine effectiveness (VE) against progression to disseminated disease via the adjusted odds ratio of vaccination among cases with lesions across multiple anatomical regions versus cases with lesions contained to a single anatomical region. Body Regions Anatomical regions of the body used to characterize lesion spread. Spread was defined>1 groups with lesions. Results Analyses included 4,613 mpox cases; 3,045 (66.0%) reported lesions disseminated across multiple anatomical regions and 1,956 (42.4%) were living with HIV infection. Among cases with disseminated lesions, 114 (3.7%) had received any pre-exposure vaccination and 43 (1.4%) received post-exposure vaccination, compared with 286 (18.2%) and 146 (9.3%), respectively, of 1,568 cases with lesions contained to a single region. VE against progression to disseminated disease was 58.9% (95% confidence interval: 50.4-65.9%) for any pre-exposure immunization with JYNNEOS, and 57.6% (46.3-66.5%) and 61.0% (47.3-71.1%), respectively, for 1 and 2 dose JYNNEOS series. VE against progression to disseminated disease was 15.9% (3.3-26.8%) for cases who received JYNNEOS only as post-exposure prophylaxis. Pre-exposure VE against progression to disseminated disease was 66.4% (56.6-74.0%) for HIV-negative cases and 45.3% (28.0-58.5%) for cases living with HIV. Proportion of Individuals with Regions Affected by Lesions The proportion of mpox cases in California in each subpopulation who reported anywhere from 1-6 body site groups, as defined in figure 2, affected with lesions. A-D represent the unvaccinated population of mpox cases, E-H is the population given PEP, and I-L the vaccinated population (either single or double vaccinated). The first column A, E and I show the HIV- negative population, B, F, and J are persons with HIV (PWH), C, G, and K are PWH with CD4 <500, and D, H, and L are PWH with CD4 ≥ 500. Conclusion All persons at risk for mpox should receive JYNNEOS vaccine series to reduce the odds of disseminated disease. Among persons infected with mpox, including those living with HIV, vaccination with JYNNEOS is associated with less severe clinical presentation. Protection was greatest when the vaccine was administered prior to exposure. Strategies are needed to ensure continuous access to JYNNEOS vaccination among all at-risk persons. VE of JYNNEOS in Preventing Lesion Spread VE of JYNNEOS for PEP, single, double, and any pre-exposure vaccination in reference to a nonvaccinated counterpart. Conditional logistic regression models matching individuals in the “all cases” category on HIV status to estimate VE given number and timing of doses received. Additionally, individuals were stratified by HIV status. All vaccinated groups were calculated in reference to an unvaccinated population. Disclosures All Authors: No reported disclosures

P-2319. A 5-year Single Center Review of Strongyloides stercoralis Seropositivity in Cardiac Transplant Candidates in Central Texas

Abstract Background Strongyloides stercoralis is a parasitic nematode that chronically infects an estimated 30 - 100 million individuals worldwide and is mainly found in tropical, subtropical, and warm temperate regions. In solid organ transplant recipients, Strongyloides can cause disseminated disease or hyperinfection, which has an extremely high mortality rate. According to the American Society of Transplantation, all potential solid organ donors and recipients with risk factors for Strongyloides infection should undergo serologic screening. Our study aimed to identify the prevalence of Strongyloides seropositivity in patients evaluated for cardiac transplantation. We also aimed to identify demographic characteristics and risk factors associated with seropositivity, and any side effects of treatment. Table 1 Total number of Strongyloides seropositive (SSp) and seronegative (SSn), total number of patients that received cardiac transplant, demographic characteristics, and country of origin. Methods This study was a single-center, retrospective chart review of patients aged 18 or older who underwent cardiac transplant evaluation and serologic screening for Strongyloides at Baylor Scott & White Medical Center in Temple, Texas, between March 2019 and March 2024. A positive test was defined as > 1.1 Index Value (IV), negative as < 1.0 IV, and equivocal as 1.0-1.1 IV. Data was collected and managed using Research Electronic Data Capture (REDCap). Bivariate analyses were completed to test the association between the Strongyloides Seropositive (SSp) and Strongyloides Seronegative (SSn) groups. All statistical analyses were performed in SAS 9.4. Table 2 Pre-transplantation serologic results SSp and SSn. Abbreviations: Herpes Simplex Virus (HSV), Cytomegalovirus (CMV), Ebstein Bar virus (EBV), Varicella Zoster Virus (VZV), Human T-lymphotropic virus-1 (HTLV-1), human immunodeficiency virus (HIV). Results 259 patients underwent screening for cardiac transplant and Strongyloides. 11.58% tested positive or equivocal for Strongyloides. Epidemiological risk factors were not associated with seropositivity. All patients who underwent cardiac transplantation received appropriate treatment with no side effects. There were no cases of disseminated infection. Table 3 Travel history to endemic including tropic regions of Southeast Asia and the Appalachian region in the US, history of homelessness, history being barefoot, symptoms at diagnosis (Gastrointestinal, cutaneous, or respiratory symptoms), and treatment history. Conclusion Our study provides insight into the prevalence of Strongylodies in Texas. Based on our results, targeted screening may miss many seropositive patients. Given the lack of epidemiological risk factors within our SSp population and rising concern for indigenous cases within Texas, we recommend consideration of universal Strongyloides screening for solid organ transplant donors and recipients. Disclosures All Authors: No reported disclosures

P-1048. Coccidioides immitis Fungemia in Central California: A 10 Year Experience

Abstract Background Coccidioides immitis is a soil-borne fungus endemic to Southwestern United States. While about 40% of patients develop symptomatic infections, disseminated infections remain rare (1-3%). Coccidioides fungemia is extremely uncommon and associated with high mortality. Previous reports on Coccidioides fungemia in the 90’s to early 2000’s, mostly from Arizona, showed affected patients had underlying immunocompromising conditions such as HIV/AIDS, and survival was poor. We aim to characterize Coccidioides immitis fungemia in our Central California population in recent years. Methods We performed a retrospective analysis of patients with Coccidioides fungemia in a major 750-bed referral center in Central California between the years of 2014 – 2024. Data was collected pertaining to demographics, comorbidities, clinical presentation, management, and outcomes. Descriptive statistics were used to analyze sample characteristics. Results We identified 11 patients with Coccidioides fungemia during the study period. The mean age of affected patients was 40 years (Table 1). Mortality was extremely high with death occurring in an overwhelming 82% of patients. Duration of symptoms was less than 1 week in 6/11 (55%) of patients. Death occurred in 44%, even before blood cultures came back positive (Table 2). Cultures returned positive within 7 days of plating in 7/11(64%) patients. Notably, 9 out of 11 patients had acute Coccidioides infection. Only 1 patient had no underlying comorbid condition (Table 3). All patients received anti-fungal therapy with either liposomal amphotericin B or fluconazole. Conclusion Coccidioides immitis fungemia continues to be a rare and fatal form of disseminated disease. The majority of patients in our cohort had acute infection, rapid progression of disease and death. Only 27% of patients in our study had HIV/AIDS, which is less than what has been documented in previous studies (which were done in the early 80s-90s). However, many patients in our cohort had other underlying immunocompromising conditions such as SLE, diabetes mellitus). Despite the advances in management of HIV/AIDS, due to increase in other immunocompromising conditions and use of immunomodulatory agents, Coccidioides fungemia remains a threat. Disclosures All Authors: No reported disclosures

P-1053. Invasive Fusariosis: 5-Year Update from a Single-Center Experience in the Voriconazole Era

Abstract Background Invasive fusariosis is a rare but aggressive infection seen in immunocompromised patients that is often multidrug resistant. The optimal therapeutic approach in the presence of elevated MICs to standard antifungal treatment remains unknown and careful monitoring of local epidemiology of this infection is needed. We performed a retrospective review of invasive fusarium infections to help guide management at our center. Methods We identified all cases of invasive Fusarium infection between January 2019 and April 2024. We collected patient characteristics, including clinical presentation, therapy, and 12-week outcomes, as well as organism speciation and susceptibility testing. Results Seven patients were diagnosed with either proven (6, 86%) or probable (1, 14%) invasive fusariosis. The median age was 60 years and six (86%) patients were male. Four (57%) had hematologic malignancies, of which 3 (75%) received stem cell transplant, 1 (14%) idiopathic neutropenia, 1 (14%) severe burns, and 1 (14%) received solid organ transplant. Four (57%) had prolonged preceding neutropenia. Cutaneous lesions were the most common presentation (5, 71%). The four cases in neutropenic hosts had cutaneous lesions with presumed or confirmed disseminated disease involving the sinuses or lung. Three (43%) received combination therapy with voriconazole and terbinafine, 2 (29%) received posaconazole, 1 (14%) received amphotericin, and 1 (14%) received voriconazole. Fusarium solani complex was the most commonly isolated species (2, 29%). Species identification was not available in 3 cases. Susceptibility testing was available in 5 (71%) cases and MICs to voriconazole were ≥16 µg/mL and to terbinafine were ≥2. All 4 cases treated with voriconazole had elevated MICs and yet exhibited a partial (2, 50%) or complete clinical response (2, 50%) to treatment. 12-week survival was seen in 4 (57%) of cases, with one patient lost to follow-up. Conclusion Mortality to invasive fusariosis is high but remains similar at our center compared to the 2002-2014 period. Diagnosis remains challenging and tissue biopsy is critical. Despite elevated MICs, clinical responses to voriconazole with or without the addition of terbinafine are observed. Disclosures All Authors: No reported disclosures

P-912. A 10-Year Retrospective, Single-Center Analysis of Nocardiosis in Immunocompetent and Immunocompromised Hosts: Clinical and Microbiological Features, Treatment Outcomes, and Determinants of Central Nervous System Involvement

Abstract Background Nocardia species are organisms with the potential to affect numerous organ systems, including the brain. However, it is unknown whether specific host or microbe factors are associated with central nervous system (CNS) nocardiosis and whether outcomes for CNS nocardiosis differ according to host immune status. Demographics and clinical characteristics by immune status. SOTr: solid organ transplant recipient. SCTr: stem cell transplant recipient. MSK: musculoskeletal structure, such as bone or joint. COPD: chronic obstructive pulmonary disease. WBC: white blood cell count. *The isolation of Nocardia in 2 or more non-contiguous body sites constituted disseminated disease Methods We performed a retrospective review of all adults admitted to Yale New Haven Hospital with laboratory-confirmed nocardiosis from 2013 to 2023. CNS involvement was defined as the identification of Nocardia spp on brain tissue or new radiological brain lesions in a patient with extra-neural nocardiosis. We performed multivariate logistic regression analyses of clinical and microbiological variables related to CNS involvement. Nocardia species distribution by CNS involvement Results 94 patients were included, of which 63 (67%) were immunocompromised (Table 1). The most common immunocompromising conditions were recipients of solid organ transplants (32%) and stem cell transplants (22%). Sixteen (17%) patients had CNS involvement of their nocardiosis; this included 22% of immunocompromised and 6% of immunocompetent patients (p=.056). The most common species isolated was the Nocardia nova complex (Table 2). Table 3 summarizes the univariate analysis of factors associated with CNS involvement. Black race [OR 3.7 (1.2-11.7), p=.03] and N. farcinica infection [OR 5.9 (1.8-19.3), p=.005] were associated with increased risk of CNS involvement. In a multivariate analysis, infection by N. farcinica was an independent risk factor for CNS involvement [OR 5.3 (1.5-18.7), p=.009]. There were no significant survival differences in immunocompromised hosts, with or without CNS disease, compared to immunocompetent hosts. Univariate analysis of demographic, host immune status and organism features associated with CNS involvement. Conclusion N. farcinica infection was identified as an independent risk factor of CNS involvement in patients with nocardiosis. Other factors related to the net state of immunosuppression were not associated with an increased risk for CNS involvement. Disclosures All Authors: No reported disclosures

P-769. A chromosome 4p14 locus associates with higher protection from Leprosy in close family contacts of Lepromatous Leprosy cases in endemic regions

Abstract Background Leprosy presents as an infectious disease with intricate genetic and immunological underpinnings. Genetic variations affecting cytokine genes and immune receptors, such as Toll-like receptor 1 (TLR1), may influence disease susceptibility. Close family contacts of individuals with slit skin positive lepromatous leprosy face a notably heightened risk of transmission. It is crucial to implement rigorous screening and early intervention protocols to promptly identify and manage latent infections, thereby curtailing potential disease dissemination within households and communities. Methods We conducted a genome-wide association study involving close family contacts of individuals with positive slit skin smears for Mycobacterium leprae. Our study comprised 131 lepromatous leprosy patients from prospective cohorts in an endemic region. Genotyping was performed using real-time polymerase chain reaction (RT-PCR) on the 7500 Real Time PCR System, employing SNP genotyping assays for pre-selected SNPs (rs7842033 and rs4167826) with specific primers and probes corresponding to the SNP of interest. Results Two-locus analyses of association of variants near rs7842033 showed a haplotype comprised of rs977477 and an IL9 missense variant, rs943138945, had the most significant association (p = 1.26x10-12).Our results showed no association between the SNP rs4052176 in NOD2 and leprosy in this population. Conclusion Situated on chromosome four (4p14), the TLR1 gene encodes a receptor that identifies glycolipids and lipopolysaccharides of M. leprae, stimulating the transcription factor nuclear factor-kappa B (NF-kβ) and enhancing the expression of pro-inflammatory genes. This gene may confer a degree of protection to close contacts against Leprosy. Disclosures All Authors: No reported disclosures

Impact of fluconazole on outcomes of patients with primary pulmonary coccidioidomycosis: a commercial health insurance claims-based, propensity score matched analysis.

Patients with pulmonary coccidioidomycosis often experience prolonged symptoms lasting weeks to months. Limited data exist regarding whether fluconazole prevents development of disseminated disease or shortens symptom duration. We describe factors associated with fluconazole receipt and assess its effect on outcomes among patients with pulmonary coccidioidomycosis. Using the MerativeTM MarketScan® Commercial Database, we identified immunocompetent patients ages 18-64 with incident pulmonary coccidioidomycosis during 2017-2023 and continuous enrollment in the 180 days before and after diagnosis. We examined demographic and clinical differences between patients treated vs. not treated with fluconazole and performed 1:1 greedy nearest neighbor propensity score matching to control for these differences. We performed bivariate analyses on the matched subset to evaluate patient outcomes by fluconazole receipt. Among 1,448 patients with pulmonary coccidioidomycosis, 659 (46%) received fluconazole. Patients who received fluconazole more frequently had pre-diagnosis symptoms (95% vs. 72%, p<0.001) and antibiotic prescriptions (68% vs. 32%, p<0.001) than those who did not. Among the propensity score matched subset (n=696), hospitalization (4% vs. 1%, p=0.004) and disseminated coccidioidomycosis (3% vs. 0%, p=0.006) were more frequent among patients who received fluconazole. The median number of days from diagnosis to last visit for chest pain (50.0 vs. 46.5), cough (64.0 vs. 39.0), fatigue (63.0 vs. 65.5), myalgia (98.0 vs. 74.0), and joint pain (93.5 vs. 107.5) was not significantly different between treatment groups. Our results support existing guidelines that fluconazole may not be associated with improved outcomes for certain immunocompetent patients with pulmonary coccidioidomycosis.

Tinea Capitis Induced by Barber Shaving: Isolation of Trichophyton tonsurans.

Background/Objective:Tinea capitis is a common scalp fungal infection with significant implications for public health, particularly in regions where proper hygiene and access to healthcare are limited. Emerging evidence suggests that this disease, particularly in young male individuals, may be related to certain unsanitary practices in barbershop settings, such as the use of contaminated shaving equipment. To increase awareness of the risk of scalp dermatophyte infections by disclosing different cases of tinea capitis that had arisen shortly after hairdressing procedures and providing a comprehensive review of the existing literature. Patients and Methods: 10 cases of young, adult male patients developed tinea capitis after haircuts carried out at different local barbershops in Sardinia. A collection of data regarding age, sex, location of the disease, clinical manifestations as well as direct microscopy and cultural investigations were performed. Results: Clinical manifestations varied among patients, exhibiting both non-inflammatory and inflammatory features, cultural investigations were positive for Trichophyton tonsurans. Patients were treated with griseofulvin or terbinafine in combination with topical antimycotics. Two cases out of the ten patients developed scarring alopecia. Conclusions: Outbreaks of T. tonsurans-induced tinea capitis, linked to hairdressing, have been recorded in many different countries. Timely diagnosis and therapy are crucial, since any delay can result in disease dissemination and potential complications such as scarring alopecia, particularly in the inflammatory forms.

The immunogenetic basis of severe herpes simplex infections in neonates and children: a review.

Human herpes simplex virus (HSV) is a double stranded DNA virus with two distinct types, HSV-1 and HSV-2. The global burden of HSV is high with an estimated 2/3 of the adult population seropositive for at least one of these types of HSV. HSV rarely causes life-threatening disease in immunocompetent children and adults. However, in neonates and children with a developmentally immature immune system it can cause disseminated disease and herpes simplex encephalitis (HSE). Recent studies in children and neonates suggest that genetic risk-factors can contribute to severe HSV phenotypes in neonates and children. In particular, genetic defects in theToll Like Receptor 3 (TLR3) signaling pathway that attenuate the type I interferon response to HSV are being increasingly recognized in children with severe phenotypes of HSV. In this review, we discuss the epidemiology and immunological aspects of HSV disease in neonates and children and provide an in-depth review of the studies characterizing the role of inborn errors in the TLR3 pathway and other immune genes in HSV. We highlight the need for future research to identify the immunogenetic basis of severe or recurrent HSV disease in neonates and children. IMPACT: Review the epidemiology and phenotypes of herpes simplex virus (HSV) infection in neonates and children. Discuss the mechanisms of immunity against HSV highlighting the developmental vulnerability of neonates and infants to severe HSV disease. Explore in depth the genes and immune pathways that underlie genetic predisposition to severe HSV disease in neonates and children, and outline strategies for multi-disciplinary clinical evaluation of severe disease.

The adoption of biosecurity measures and its influencing factors in Bangladeshi layer farms

Developing nations like Bangladesh are particularly vulnerable to poultry diseases, notably Highly Pathogenic Avian Influenza. Adopting biosecurity approaches that assist farms in disease control and prevention can decrease the industry-wide dissemination of infectious diseases. In light of these factors, this study was carried out to investigate the implementation of biosecurity practices on layer farms in Bangladesh. Using a stratified random sample method, a total of 315 layer farms from fourteen upazilas (sub-districts) in seven districts were surveyed using a semi-structured interview schedule. The study explored layer farmers' experiences with biosecurity procedures adopted on farms that included equipment, employees, and visitors. The study found that the overall biosecurity score was 72.5 out of 100. It was concluded that internal biosecurity was better than external biosecurity. The study also revealed that layer farms have a larger proportion of partial adopters based on the adoption index. The application of the Tobit model identifies that education, farming experience, attitude towards risk, price of layer sheds, return from layer production, and access to biosecurity knowledge had a substantial influence on adopting biosecurity measures. The findings might be helpful for farmers and policymakers to ensure the required modifications to improve compliance with biosecurity protocols and could assist relevant authorities in implementing particular biosecurity initiatives.

Assessing the Role of Vaccination in the Control of Hand, Foot, and Mouth Disease Transmission

The impact of vaccination on the dynamics of hand, foot, and mouth disease (HFMD) transmission is explored in this paper, considering a fractional-order derivative system of equations. This model provides vaccination strategies and characterizes local and global stability using Lyapunov functions. This work computes the basic reproduction number (R0) to represent the endemic and epidemic scenarios. Additionally, sensitivity analysis was performed to identify the most critical parameters responsible for the disease dissemination. Our results indicate that vaccination plays a crucial role in controlling HFMD, significantly reducing its prevalence. These findings align with existing research, supporting the importance of effective vaccination strategies and public health interventions against HFMD. The fractional-order model captures the memory effect in infectious disease dynamics, providing further insight into modeling HFMD transmission compared to a traditional integer-order model. The results would contribute to effective vaccination strategies and public health interventions against HFMD.

Severe Non-Donor-Derived Lymphocytic Choriomeningitis Virus Infection in 2 Solid Organ Transplant Recipients.

Lymphocytic choriomeningitis virus (LCMV) infection in immunocompromised hosts can result in disseminated disease, meningoencephalitis, and death. Published cases in transplant recipients have been traced to transmission from infected donors. We report 2 cases of serious, non-donor-derived LCMV infection in solid organ transplant recipients. Initial identification of LCMV infection was done by using metagenomic next-generation sequencing (mNGS). Subsequent evaluations and confirmatory testing involved molecular diagnostics, serology, and phylogenetic analysis. A detailed epidemiologic investigation was conducted. LCMV was detected by mNGS in 2 solid organ transplant recipients from distinct donors. A heart transplant recipient (from donor 1) died of progressive, disseminated LCMV infection, while a kidney transplant recipient (from donor 2) with LCMV meningoencephalitis survived. A multistate laboratory and epidemiologic investigation of both donors and all their organ recipients was initiated. Postmortem samples were obtained from both donors, and pretransplant and/or posttransplant samples were obtained from 5 of the 6 organ recipients. mNGS, serologic, and real-time reverse-transcription polymerase chain reaction testing confirmed LCMV infection in both solid organ transplant recipients. Epidemiologic investigation revealed significant pretransplant rodent exposures for both LCMV-infected recipients. Laboratory studies for the other organ recipients from both donors were negative for LCMV infection. Our investigations suggest that LCMV infection in 2 solid organ transplant recipients originated from rodent exposure preceding transplantation and were not donor derived. Although uncommon, healthcare providers should be aware of LCMV-associated serious and life-threatening illness in immunocompromised hosts. Diagnostic modalities are limited to reference laboratories.

Effect of suboptimal growing conditions induced by agroecological practices on the yield of 12 Cavendish banana cultivars

Summary In the French West Indies (FWI), practices alternative to chemical inputs are implemented to improve the sustainability of banana cropping systems. These agroecological practices are based on organic fertilization, soil covering with weed live mulch and severe prophylactic deleafing to limit sigatoka disease dissemination. However, these practices may impair the availability of soil mineral nutrients and the photosynthetic capacity of the plant and consequently induce suboptimal plant growth conditions. To assess the performance of the different banana cultivars from the Cavendish group in these suboptimal conditions, the yield components of 12 Cavendish banana cultivars were compared with four crop management modalities: i) high mineral fertilization, chemical weed control and minimum prophylactic deleafing (N + L+), ii) high mineral fertilization, chemical weed control and severe prophylactic deleafing (N + L−), iii) low organic fertilization, weed live mulch and minimum prophylactic deleafing (N−L+) and iv) low organic fertilization, weed live mulch and severe prophylactic deleafing (N−L−). The performance of all cultivars varied according to the crop management modalities in the following order: N + L+ &gt; N + L− &gt; N−L+&gt; N−L−. However, the hierarchical order among the cultivars differed according to the crop management modality. Cultivar Americani exhibited the best performance in non-limiting conditions. Cultivars such as Ruby, Gua01 and Mat12 performed better with severe prophylactic deleafing while Gua02 and Ruby performed better with the low soil nutrient availability induced by organic fertilization and weed live mulch. These results can be used to guide the choice of Cavendish cultivar according to production constraints, particularly with regard to agroecological practices or abiotic stresses, such as reduced photosynthesis or limited nitrogen resource. These results suggest that there is a variability in the tolerance to abiotic stresses between the cultivars of the Cavendish group.

IMPACTS OF CLIMATE CHANGE ON LIVESTOCK HEALTH AND WELFARE IN NIGERIA'S NORTH-EAST REGION

This paper studies the influence of climate change on health and welfare in Nigerian North-East livestock, covering direct and indirect impacts. An increased temperature, changing patterns of precipitation, and an increased humidity culminate into heat stress affecting the physiology, behaviour, and productivity of the livestock.Long-term exposure to extreme heat reduces feed intake, reproductive performance, and immune function due to metabolic disorders, oxidative stress, and increased vulnerability to diseases. Besides, climatic changes favored the dissemination of vector-borne diseases, such as trypanosomiasis and Rift Valley fever, further compromising the health status of livestock and creating zoonotic risks in humans.It also cites nutritional problems caused by higher fungal proliferation caused by climate and leading to mycotoxicoses in feeds. Such changes add pressure on the livelihoods of those depending on the livestock, especially small-scale farmers, who incur enhanced veterinary costs and mortality hence reducing food security.The impact is deep at the socio-economic level, as livestock farming is one of the most important sources of income and sustenance in the region. Thus, the paper calls for a multidimensional adaptive approach through improvements in the management of livestock, nutritional interventions, vector control, and disease surveillance systems to mitigate such challenges. This therefore further underlines the importance of policy development and community involvement in creating resilience and thus assuring a sustainable livestock farming system in the face of a changing climate. It is expected that these findings will inform policy, researchers, and other stakeholders on how to build adaptive capacity within the livestock sector in order to secure livelihoods and improve food security in Northeast Nigeria.

Multidimensional perspectives of geo-epidemiology: from interdisciplinary learning and research to cost-benefit oriented decision-making.

Research typically promotes two types of outcomes (inventions and discoveries), which induce a virtuous cycle: something suspected or desired (not previously demonstrated) may become known or feasible once a new tool or procedure is invented and, later, the use of this invention may discover new knowledge. Research also promotes the opposite sequence-from new knowledge to new inventions. This bidirectional process is observed in geo-referenced epidemiology-a field that relates to but may also differ from spatial epidemiology. Geo-epidemiology encompasses several theories and technologies that promote inter/transdisciplinary knowledge integration, education, and research in population health. Based on visual examples derived from geo-referenced studies on epidemics and epizootics, this report demonstrates that this field may extract more (geographically related) information than simple spatial analyses, which then supports more effective and/or less costly interventions. Actual (not simulated) bio-geo-temporal interactions (never captured before the emergence of technologies that analyze geo-referenced data, such as geographical information systems) can now address research questions that relate to several fields, such as Network Theory. Thus, a new opportunity arises before us, which exceeds research: it also demands knowledge integration across disciplines as well as novel educational programs which, to be biomedically and socially justified, should demonstrate cost-effectiveness. Grounded on many bio-temporal-georeferenced examples, this report reviews the literature that supports this hypothesis: novel educational programs that focus on geo-referenced epidemic data may help generate cost-effective policies that prevent or control disease dissemination.

Ocular adnexal lymphoma - A single-center observational study of survival outcomes.

This study aims to comprehensively characterize the clinical, demographic, and histopathological features of ocular adnexal lymphoma (OAL) and assess their impact on patients' survival outcomes. A total of 123 patients were included in the study; of these, 93 patients were selected for survival analysis. Survival data were analyzed using the Kaplan-Meier test, and correlation was assessed through the log-rank test and Cox regression analysis. The median age at presentation was 56 years. Furthermore, 98% of patients had primary OAL. The orbit was the most common site of involvement. The majority of patients were of B-cell origin (98%), and only 2% of patients had T-cell lymphoma. In addition, 83% of patients were treated with chemotherapy, and with a median follow-up of 38 months, complete remission was achieved in 48% of patients. The median progression-free survival was 26.4 months. The presence of disseminated disease was strongly linked to an unfavorable prognosis (P < 0.001) and reduced survival (P = 0.037). The 5-year overall survival of the entire study cohort was 81%. The prognosis for OAL is found to be favorable, but the presence of dissemination serves as a notable predictor for poor prognosis.