Disseminated Disease Research Articles

Tackling Histoplasmosis Infection in People Living with HIV from Latin America: From Diagnostic Strategy to Public Health Solutions.

Histoplasmosis, caused by the thermally dimorphic fungus Histoplasma spp., is a disease with a broad clinical spectrum, presenting from asymptomatic/flu-like symptoms to progressive disseminated disease in people with immunosuppression. In recent years, the concept of histoplasmosis as a disease restricted to the American continent has changed, as now histoplasmosis is reported in many regions around the world. In Latin America, histoplasmosis represents a threat, especially in people with advanced HIV disease (AHD). Diagnosis of histoplasmosis in people living with HIV (PLHIV) is challenging due to the low index of suspicion of the disease, non-specificity of signs and symptoms, and limited access to specific laboratory testing, while the diagnostic delay is significantly associated with mortality. In the last decade, novel diagnostic tests have been developed for the rapid detection of histoplasmosis, such as commercial kits for antigen detection. Furthermore, advocacy groups were created that presented histoplasmosis as a public health problem, with emphasis on patients at risk of progressive disseminated disease. This review aims to discuss the impact of histoplasmosis associated with AHD in Latin America and the strategies employed to tackle histoplasmosis, from the implementation of laboratory testing to disease advocacy and public health interventions.

Protocol of a scoping review of systematic reviews and meta-analyses about COVID-19 vaccines and associated adverse events from vaccination.

The continuous dissemination of coronavirus disease of 2019 (COVID-19) literature can inform decision-makers and the public. Since the widespread use of COVID-19 vaccines, more systematic reviews have summarized the effectiveness and reported adverse events associated with vaccination. Previous systematic and scoping reviews on COVID-19 summarized various aspects surrounding COVID-19, however, a scoping review is needed to summarize the characteristics of COVID-19 vaccines and associated adverse events reported in systematic reviews and meta-analyses to provide comprehensive evidence for informed medical decision-making. We will conduct a scoping review concerning COVID-19 vaccines and adverse events from vaccines. We will search from December 2019 to present in Epistemonikos, Campbell Library, CINAHL (Ovid), MEDLINE (Ovid), Scopus, CENTRAL (Ovid), Web of Science, WHO COVID-19 database, Joanna Briggs Institute of Excellence, and COVID-19 Evidence Reviews resource. We will include systematic reviews, meta-analyses, or both of randomized controlled trials and observational studies and exclude individual randomized controlled trials and observational studies. Abstracts and full-texts will be screened prior to selection. Investigators will independently use a calibrated quantitative and qualitative data extraction sheet and rate the quality of articles with AMSTAR, resolving disagreements to aim for good agreement (≥80%). An updated scoping review of the characteristics and safety of COVID-19 vaccines would highlight the accuracy of the evidence to inform decision-making concerning COVID-19 vaccination.

A Case of Multiple Gastrointestinal Ulcer: A Rare Presentation of Strongyloidiasis

Strongyloides stercolaris is a common intestinal nematode in tropical and subtropical countries like Bangladesh. The presentation of this infection is nonspecific. Mostly it remains asymptomatic with peripheral eosinophilia. Immunocompromised individuals are at high risk of hyper infection to disseminated disease. We present a case of Strongyloides in an immunocompetent patient with features of gastric outlet obstruction. Laboratory findings revealed hypereosinophilia with multiple gastrointestinal ulcers on endoscopy. Biopsy was taken from a gastric ulcer which revealed ulceration and dense infiltration of acute and chronic inflammatory cells along with extensive intestinal metaplasia. There were tiny helminthic bodies within the mucosal glands and on the surface consistent with Strongyloides stercoralis. Routine examination of stool also revealed larvae of Strongyloides stercolaris. J Dhaka Med Coll. 2022; 31(1) : 163-166

Implementation of biosecurity measures by hoof trimmers in Switzerland

Biosecurity in livestock farming includes all measures preventing pathogen introduction onto a farm (external biosecurity) and pathogen transmission on the farm itself (internal biosecurity). An important risk factor for the dissemination of infectious diseases are specialised external persons working on numerous farms, such as professional hoof trimmers in Switzerland. In the present study, 49 hoof trimmers, participating in the Swiss claw health programme and working as professionals, were questioned regarding their biosecurity measures and observed by two veterinarians during hoof trimming in order to assess the implementation of biosecurity measures by hoof trimmers. Data were processed using a scoring system, in which points were allocated to the different working methods taking into account their assumed transmission potential for infectious diseases such as digital dermatitis (DD) and Salmonellosis. The working method, which complied with the ideal biosecurity measure, was always given a whole point, whereas less optimal working methods were only given an intermediate value or no point. The scoring system helped identify precisely the strengths and weaknesses of the hoof trimmers in terms of biosecurity. The level of implementation of biosecurity measures by hoof trimmers was overall quite low (53 %=average of the overall biosecurity scores of the 49 hoof trimmers). Hoof trimmers which attended specialised training courses tended to have a higher level of implementation of biosecurity measures. The answers given by the hoof trimmers and the observations made by the veterinarians were compared, whereby it was found that hoof trimmers generally evaluated themselves better in regard to biosecurity than veterinarians assessed them. In summary and based on the results of this study, the dissemination of pathogens, such as DD associated treponemes and salmonella is possible during hoof trimming performed by external persons working on numerous farms. Thus, future training and continuing education courses should place emphasis on biosecurity.

Dispersal engendered synchronization and stability of mediated infectious diseases in the patchy environment using mean-field diffusive coupling

Mobility of humans and mediating agents significantly affects the scope of mediated infectious diseases. The spatial transmission of mediated infectious diseases ultimately depends on the movement of hosts and mediators. To comprehend the causes, predict, evaluate, and restrict epidemic transmission, it is crucial to investigate the dynamics of mediated infectious diseases in the presence of mobility. The network of mediators and the host metapopulation are related to the spatial coupling for disease dissemination. Thus, in this article, the metapopulation dynamics of the mediated infectious disease model is studied in a patchy environment where the hosts and mediators population is divided into sub-population. Two networks are used to represent the patchy environment: the hosts or humans network and the mediators network. Mean field diffusive coupling is used to connect the network patches. Both homogeneous and heterogeneous networks are investigated in terms of dynamics. Dispersal engenders the patches of corresponding networks to synchronize and reach bistable states of non-trivial amplitude death. Numerical simulations are performed to demonstrate the change from one state to another state, caused by transcritical bifurcation. The stability of disease free equilibrium and endemic equilibrium is also determined by the reproduction number R0.

Cutaneous Mycobacterium szulgai infection in a patient with Cushing's syndrome: a case report and literature review

BackgroundOpportunistic infection is an under-recognized complication of Cushing’s syndrome, with infection due to atypical mycobacterium rarely reported. Mycobacterium szulgai commonly presents as pulmonary infection, with cutaneous infection seldom reported in the literature.Case Presentation48-year-old man with a newly-diagnosed Cushing’s syndrome secondary to adrenal adenoma presented with a subcutaneous mass on the dorsum of his right hand, was diagnosed with cutaneous Mycobacterium szulgai infection. The most likely source of the infection was through minor unnoticed trauma and inoculation from a foreign body. The patient’s Cushing’s syndrome, high serum cortisol levels and secondary immune suppression facilitated mycobacterial replication and infection. The patient was successfully treated with adrenalectomy, surgical debridement of cutaneous lesion, and a combination of rifampicin, levofloxacin, clarithromycin, and ethambutol for 6 months. There were no signs of relapse one year after cessation of anti-mycobacterial treatment. A literature review on cutaneous M. szulgai infection to further characterize the clinical characteristics of this condition, identified 17 cases of cutaneous M. szulgai infection in the English literature. Cutaneous M. szulgai infections with subsequent disease dissemination are commonly reported in immunocompromised hosts (10/17, 58.8%), as well as in immunocompetent patients with a history of breached skin integrity, such as invasive medical procedures or trauma. The right upper extremity is the most commonly involved site. Cutaneous M. szulgai infection is well controlled with a combination of anti-mycobacterial therapy and surgical debridement. Disseminated infections required a longer duration of therapy than localized cutaneous infections. Surgical debridement may shorten the duration of antibiotics.ConclusionsCutaneous M. szulgai infection is a rare complication of adrenal Cushing’s syndrome. Further studies are needed to provide evidence-based guidelines on the best combination of anti-mycobacterial and surgical therapy for managing this rare infective complication.

Cather-related Aspergillus Fungemia: Case Report and Literature Review.

Aspergillus fungemia is encountered infrequently in clinical practice, even in the setting of invasive and disseminated disease. Prolonged Aspergillus fungemia secondary to a central venous catheter is notably rarer. We describe the case of a 13-year-old boy with Aspergillus fungemia in the setting of a central venous catheter who was found to have pulmonary aspergillosis upon evaluation. We reviewed the literature for published cases of catheter-related Aspergillus fungemia and summarized the findings. We also sought to differentiate true fungemia from pseudofungemia and explored the clinical significance of aspergillemia. We found 6 published cases of catheter-related Aspergillus fungemia in addition to the 1 discussed in this report. Based on the review of case findings, we propose an algorithm for an approach to a patient with a positive blood culture for Aspergillus spp. True aspergillemia is infrequent even in the setting of disseminated aspergillosis among immunocompromised patients and the presence of aspergillemia does not necessarily portend more severe clinical disease course. The management of aspergillemia should involve a determination of the possibility of contamination, and if deemed genuine, a thorough workup to define the extent of the disease process. Treatment durations should be based on tissue sites of involvement and could be shorter in the absence of tissue-invasive disease.

Factors attributed to depressive symptoms in women coping with infertility during the pandemic of COVID-19

Link of Video Abstract: https://youtu.be/2L4njgfd3SE Background: The dissemination of coronavirus disease (COVID-19) has led to delayed infertility treatment and fear of contracting the virus which can affect the mental status of women with infertility. This research aimed to investigate whether fear, depression, perceptions, and knowledge related to COVID-19 affected infertility patients in seeking treatment and analyzed factors associated with depression during COVID-19 pandemic. Method: This is a cross-sectional study utilizing an electronic survey distributed to infertility patients attending fertility services between May and July 2021. The primary outcomes were demographic characteristics, clinical parameters of infertility, depressive symptoms based on the Patient Health Questionnaire-9 (PHQ-9) score, and fear of COVID-19 scale (FCV-1 and FCV-2). Results: A total of 533 patients were included. The fear of infertility treatment suspension due to COVID-19 was perceived by 34.1% of patients. The mean Patient Health Questionnaire-9 (PHQ-9) score was 4.55 ± 4.248, with mild depression occurring in 33.4% of patients. Low income, delayed treatment, and fear of COVID-19 scale (FCV-1) score together could significantly predict depression status. Despite the pandemic, 94.7% of patients decided to continue the treatment. Conclusion: The COVID-19 pandemic has given rise to stressors that may aggravate the psychological condition of women with infertility. However, the enthusiasm to continue the treatment remains undisturbed. It is imperative to offer emotional support and address the consequences of COVID-19 infection in women with infertility during the pandemic era.

A Case of Disseminated Cryptococcus Post-Kidney Transplant

Cryptococcosis is a common invasive fungal infection in solid organ transplant recipients (SOTR) that can be challenging to manage. We discuss a case of disseminated cryptococcosis in a transplant recipient. A 26-year-old woman with a history of ESRD from C1q nephropathy, living-related kidney transplant in early 2012, and allograft nephrectomy in 2015, received a deceased donor kidney transplant (DDKT). Induction after the first transplant was anti-thymocyte globulin (ATG) and maintenance immunosuppression (IS) included tacrolimus (TAC), mycophenolate (MMF), and prednisone. In December 2014, she developed nephrotic range proteinuria due to recurrent FSGS failing plasmapheresis and Intravenous immunoglobulin leading to advanced chronic kidney disease and dialysis dependence. MMF was held due to Cytomegalovirus (CMV) DNAemia. In January 2015, she developed bilateral, painful leg ulcers. Skin biopsy, spinal fluid analysis, and culture were positive for <em>Cryptococcus neoformans.</em> She was treated with liposomal Amphotericin B (LAB) for 3 weeks and 5 doses of flucytosine (5FC) followed by maintenance oral fluconazole with recurrence requiring resumption of LAB and 5FC. The patient underwent a transplant nephrectomy in May 2015 following which IS, LAB, and 5FC were discontinued and maintenance fluconazole initiated. In 2018, another skin biopsy revealed a recurrence. Maintenance antifungal was switched to itraconazole based on fungal isolate minimum inhibitory concentration (MIC) leading to remission that persisted through subsequent DDKT in August 2022. Induction IS was ATG and maintenance included TAC, MMF, and prednisone. The post-transplant course was complicated by delayed graft function requiring dialysis for about three weeks, followed by renal recovery. She continues maintenance of itraconazole under the supervision of a transplant infectious disease specialist and <em>cryptococca</em>l disease remains in remission. IS reduction or complete withdrawal is important in managing disseminated cryptococcosis in SOTR. Management of disseminated disease may require an extended course of LAB, 5FC, and maintenance azole based on MIC.

Langerhans cell hystiocytosis mimicking necrotizing ulcerative periodontitis - A case report

Langerhans cell histiocytosis (LCH) is a rare disease characterized by abnormal proliferation of bone marrow derived histiocytes followed by their deposition in tissues elsewhere in the body causing damage. Oral manifestations of LCH can sometimes be the only presenting symptoms or the first sign of a disseminated disease. Ulcerated lesions of oral mucosa are one of the common clinical manifestations and can help in early diagnosis of the disease when presented. Since the clinical features mimics several other diseases of oral and maxillofacial region it can be misdiagnosed easily as other pathologies. This article highlights the clinicopathological features of a case of LCH in an elderly patient who has reported to our outpatient department.

Abstract CT060: ACTION: A randomized phase 3 study of dordaviprone (ONC201) in patients with newly diagnosed H3 K27M-mutant diffuse glioma

Abstract Background: H3 K27M-mutant diffuse midline glioma is a universally fatal malignancy primarily affecting children and young adults. While radiotherapy (RT) provides transient benefit, no effective systemic therapy is currently available and current standard of care is RT followed by monitoring. Dordaviprone (ONC201), a first-in-class imipridone, is an oral, blood-brain barrier penetrating, selective small molecule antagonist of dopamine receptor D2/3 (DRD2) and agonist of the mitochondrial protease ClpP. An integrated pooled analysis of five open-label trials previously demonstrated efficacy in dordaviprone-treated patients with recurrent disease. This phase 3 trial will be the first randomized, controlled study evaluating dordaviprone in patients with H3 K27M-mutant disease. Methods: ACTION (NCT05580562) is a randomized, double-blind, placebo-controlled, parallel-group, international Phase 3 study of dordaviprone in patients with newly diagnosed H3 K27M-mutant diffuse glioma. Patients who have completed standard frontline radiotherapy will be randomized 1:1:1 to receive placebo, once-weekly dordaviprone, or twice-weekly dordaviprone on two consecutive days. Primary efficacy endpoints are overall survival (OS) and progression-free survival (PFS) in all participants; PFS will be assessed by response assessment in neuro-oncology-high grade glioma by blind independent central review. Other objectives include assessments of safety, additional efficacy endpoints, clinical benefit, quality of life, pharmacokinetics, biomarkers, and healthcare resource utilization. Eligible patients will have histologically confirmed H3 K27M-mutant diffuse glioma, a Karnofsky/Lansky performance status ≥70, and completed first-line radiotherapy. Eligibility will not be restricted based on age; however, patients must be ≥10 kg at time of randomization. Patients with a primary spinal tumor, diffuse intrinsic pontine glioma, leptomeningeal disease, or cerebrospinal fluid dissemination are not eligible. ACTION is currently enrolling in the United States, with additional sites to be open internationally in 2023. Citation Format: Isabel Arrillaga-Romany, Andrew Lassman, Susan L. McGovern, Sabine Mueller, Louis B. Nabors, Martin van den Bent, Michael Vogelbaum, Joshua E. Allen, Allen S. Melemed, Rohinton S. Tarapore, Dewen Yang, Patrick Wen, Timothy Cloughsey. ACTION: A randomized phase 3 study of dordaviprone (ONC201) in patients with newly diagnosed H3 K27M-mutant diffuse glioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT060.

Metabolic pathways that permit Mycobacterium avium subsp. hominissuis to transition to different environments encountered within the host during infection.

M. avium subsp. hominissuis (M. avium) is an intracellular, facultative bacterium known to colonize and infect the human host through ingestion or respiratory inhalation. The majority of pulmonary infections occur in association with pre- existing lung diseases, such as bronchiectasis, cystic fibrosis, or chronic obstructive pulmonary disease. M. avium is also acquired by the gastrointestinal route in immunocompromised individuals such as human immunodeficiency virus HIV-1 patients leading to disseminated disease. A hallmark of M. avium pulmonary infections is the ability of pathogen to form biofilms. In addition, M. avium can reside within granulomas of low oxygen and limited nutrient conditions while establishing a persistent niche through metabolic adaptations. Bacterial metabolic pathways used by M. avium within the host environment, however, are poorly understood. In this study, we analyzed M. avium proteome with a focus on core metabolic pathways expressed in the anaerobic, biofilm and aerobic conditions and that can be used by the pathogen to transition from one environment to another. Overall, 3,715 common proteins were identified between all studied conditions and proteins with increased synthesis over the of the level of expression in aerobic condition were selected for analysis of in specific metabolic pathways. The data obtained from the M. avium proteome of biofilm phenotype demonstrates in enrichment of metabolic pathways involved in the fatty acid metabolism and biosynthesis of aromatic amino acid and cofactors. Here, we also highlight the importance of chloroalkene degradation pathway and anaerobic fermentationthat enhance during the transition of M. avium from aerobic to anaerobic condition. It was also found that the production of fumarate and succinate by MAV_0927, a conserved hypothetical protein, is essential for M. avium survival and for withstanding the stress condition in biofilm. In addition, the participation of regulatory genes/proteins such as the TetR family MAV_5151 appear to be necessary for M. avium survival under biofilm and anaerobic conditions. Collectively, our data reveal important core metabolic pathways that M. avium utilize under different stress conditions that allow the pathogen to survive in diverse host environments.

A foot and mouth disease ranking of risk using cattle transportation.

Foot-and-mouth disease (FMD) is a highly infectious condition that affects domestic and wild cloven-hoofed animals. This disease has substantial economic consequences. Livestock movement is one of the primary causes of disease dissemination. The centrality properties of the livestock mobilization transportation network provide valuable information for surveillance and control of FMD. However, the same transportation network can be described by different centrality descriptions, making it challenging to prioritize the most vulnerable nodes in the transportation network. This work considers the construction of a single network risk ranking, which helps prioritize disease control measurements. Results show that the proposed ranking constructed on 2016 livestock mobilization data may predict an actual outbreak reported in the Cesar (Colombia) region in 2018, with a performance measured by the area under the receiver operating characteristic curve of 0.91. This result constitutes the first quantitative evidence of the predictive capacity of livestock transportation to target FMD outbreaks. This approach may help decision-makers devise strategies to control and prevent FMD.

Unveiling the paths of COVID-19 in a large city based on public transportation data

Human mobility plays a key role in the dissemination of infectious diseases around the world. However, the complexity introduced by commuting patterns in the daily life of cities makes such a role unclear, especially at the intracity scale. Here, we propose a multiplex network fed with 9 months of mobility data with more than 107 million public bus validations in order to understand the relation between urban mobility and the spreading of COVID-19 within a large city, namely, Fortaleza in the northeast of Brazil. Our results suggest that the shortest bus rides in Fortaleza, measured in the number of daily rides among all neighborhoods, decreased approx 25% more than the longest ones after an epidemic wave. Such a result is the opposite of what has been observed at the intercity scale. We also find that mobility changes among the neighborhoods are synchronous and geographically homogeneous. Furthermore, we find that the most central neighborhoods in mobility are the first targets for infectious disease outbreaks, which is quantified here in terms of the positive linear relation between the disease arrival time and the average of the closeness centrality ranking. These central neighborhoods are also the top neighborhoods in the number of reported cases at the end of an epidemic wave as indicated by the exponential decay behavior of the disease arrival time in relation to the number of accumulated reported cases with decay constant lambda approx 33 days. We believe that these results can help in the development of new strategies to impose restriction measures in the cities guiding decision-makers with smart actions in public health policies, as well as supporting future research on urban mobility and epidemiology.

Low-grade malt lymphoma of the nasopharynx in young adults: Successful treatment of a rare diagnosis at a rare site by radiotherapy.

Mucosa Associated Lymphoid Tissue (MALT) lymphoma is the third most common subgroup of Non-Hodgkin's lymphoma and is the most common type of primary extranodal lymphoma. They are rarely found in the nasopharyngeal region and their mean age at presentation is the sixth decade of life. We present the clinical, pathological, treatment and 5-year follow-up data of 5 cases of nasopharyngeal MALT lymphoma treated with definitive radiotherapy at our hospital, between 2009 and 2011. The average age of diagnosis was 27 years which is more than a decade earlier than what has been reported previously. Clinical symptoms included nasal obstruction, tinnitus and hearing loss. All five patients had locoregional disease. They were treated by definitive radiotherapy to a dose between 30 to 40 Gy. At 5 years of follow-up, 4 patients were in complete remission while one had disease relapse. The younger age of presentation compared to older reports in this rare subsite was an interesting finding in our study. The authors speculate that rising levels of particulate air pollution may have played a part in the etiology in this younger population. Our series shows that despite the younger age, the disease displays an indolent course and responds well to radiotherapy alone as the primary treatment. Recurrence or disseminated disease is also highly treatable with systemic chemotherapy.

Identification of immunotherapy and radioimmunotherapy targets on desmoplastic small round cell tumors.

Development of successful antibody-based immunotherapeutic and radioimmunotherapeutic strategies rely on the identification of cell surface tumor-associated antigens (TAA) with restricted expression on normal tissues. Desmoplastic small round cell tumor (DSRCT) is a rare and generally neglected malignancy that primarily affects adolescent and young adult males. New therapies capable of treating disseminated disease are needed for DSRCT, which is often widespread at diagnosis. We used immunohistochemistry (IHC) on fresh frozen surgical specimens and patient-derived xenograft (PDX) tumors and flow cytometry on DSRCT cell lines to evaluate expression of TAAs in these tumors. In vitro cytotoxicity assays were used to evaluate the efficacy of T cell-engaging bispecific antibodies (T-BsAbs) directed at these targets. In vivo, we used an intraperitoneal xenograft mouse model of DSRCT to test T-BsAbs against several TAAs. In DSRCT specimens we found widespread expression of B7-H3, EGFR, GD2, HER2, mesothelin, and polysialic acid, clinical targets for which specific antibody therapeutics are available. The expression of B7-H3, EGFR, HER2, and mesothelin was confirmed on the cell surface of DSRCT cell lines. In vitro cytotoxicity assays confirmed the efficacy of T cell-engaging bispecific antibodies (T-BsAbs) directed at these targets against DSRCT cells. Remarkably, a HER2xCD3 T-BsAb was capable of completely shrinking established tumors in an intraperitoneal mouse model of DSRCT. We propose that these TAAs should be further investigated in preclinical models as targets for immunotherapy and radioimmunotherapy with the hope of providing a rationale to extend these therapies to patients with advanced DSRCT.

Plasma small‐extracellular vesicles enriched in miR‐122‐5p promote disease aggressiveness in pediatric anaplastic large‐cell lymphoma

Plasma small‐extracellular vesicles enriched in miR‐122‐5p promote disease aggressiveness in pediatric anaplastic large‐cell lymphoma

Abstract 6395: Atovaquone promotes release of damage-associated molecular patterns from epithelial ovarian cancer cells

Abstract Epithelial ovarian cancer (EOC) is the deadliest gynecologic cancer in the United States. Most patients are diagnosed with EOC at advanced stages and have limited treatment options. Developing new therapies that are effective against localized and disseminated disease is imperative. Unfortunately, clinical trials evaluating immunotherapies in EOC have not been consistently effective. Preclinical data have shown that neoadjuvant chemotherapy can help increase antigen presentation and T cell infiltration, as well as decrease immunosuppressive effectors, suggesting that combining cytotoxic chemotherapy with immunotherapies can be a powerful approach to potentiate antitumor responses in EOC. However, studies looking at the combination of immunotherapies with carboplatin and paclitaxel, which are the mainstay chemotherapies for EOC, have not improved progression-free survival rates. We propose a novel combination approach using the well-tolerated, FDA-approved, oxidative phosphorylation (OXPHOS) inhibitor atovaquone as a sensitizer to cellular immunotherapies for EOC. OXPHOS inhibition leads to oxidative stress, which in turn leads to DNA and protein damage, activation of stress response pathways, and ultimately cell death. During cell injury and death, Damage-Associated Molecular Patterns (DAMPs) can be released into the extracellular environments, activate the innate immune system, and lead to immunogenic cell death. We have previously shown that atovaquone leads to increased reactive oxygen species levels and DNA damage. Thus, we hypothesized that atovaquone treatment would lead to release of DAMPs, including HMGB1 and TFAM, from EOC cells. Following treatment with atovaquone, we collected the supernatant of EOC cell cultures at different timepoints and measured HMGB1 and TFAM concentrations via enzyme-linked immunosorbent assays (ELISAs). We observed that both HMGB1 and TFAM concentrations were elevated at 24 and 48 hours following atovaquone treatment. This suggests that atovaquone can facilitate immune detection and attack by promoting DAMPs release. When DAMPs are released into the extracellular environment, they are recognized by innate immune cells, which become activated to produce pro-inflammatory cytokines and increase antigen presentation to T cells. Given our results showing increased release of DAMPs following exposure to atovaquone, we are developing an in vitro culture system to study immune cell responses to atovaquone-treated EOC cells. We are also monitoring transcriptomic responses of EOC cells treated with atovaquone to identify changes in expression of DAMPs and other immune-activating pathways through RNA sequencing. Our ultimate goal is to test T cell recognition and responses toward atovaquone-treated EOC cells with the intention of utilizing this chemotherapeutic agent as an adjunct to immunotherapeutic efforts for EOC. Citation Format: Mayra A. Betancourt Ponce, Nicha Boonpattrawong, Sejal Sharma, Jenny Gumperz, Manish Patankar, Lisa Barroilhet. Atovaquone promotes release of damage-associated molecular patterns from epithelial ovarian cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6395.

Nocardia pseudobrasiliensis Co-infection in SARS-CoV-2 Patients.

During the SARS-CoV-2 pandemic, few cases of Nocar-dia spp. co-infection have been reported during or after a COVID-19 infection. Nocardia spp. are gram-positive aerobic actinomycetes that stain partially acid-fast, can infect immunocompromised patients, and may cause dis-seminated disease. We report the case of a 52-year-old immunocompromised man who had Nocardia pseudobrasiliensis pneumonia develop after a SARS-CoV-2 in-fection. We also summarize the literature for no-cardiosis and SARS-CoV-2 co-infections. Nocardia spp. infection should remain a part of the differential diagnosis for pneumonia in immunocompromised hosts, regardless of other co-infections. Sulfonamide/carbapenem combina-tions are used as empiric therapy for nocardiosis; species identification and susceptibility testing are required to se-lect the optimal treatment for each patient.

Histoplasmosis in nasopharynx clinically mistaken for nasopharyngeal malignancy

Abstract Histoplasmosis is a rare type of fungal infection which may manifest as a respiratory disease or as a disseminated infection. It is common in immunocompromised patients and, in recent times, seen in association with COVID-19. On histopathological examination, many intracellular and extracellular yeast forms are seen, which can be confirmed by fungal stains. Histoplasmosis involving the nasopharyngeal region is quite rare. Till date, only less than 100 cases of pharyngo-laryngeal histoplasmosis have been reported. Such cases are clinico-radiologically easily and frequently mistaken for malignancy. Here, we report a case that initially had COVID-19-like symptoms and later presented with a nasopharyngeal mass clinico-radiologically mistaken as a nasopharyngeal malignancy. The diagnosis was established on histopathological examination and the patient recovered completely with anti-fungal treatment. A high grade of suspicion and thorough histopathological examination, especially in immunocompromised patients, complimented by fungal special stains is quite rewarding as even a disseminated disease is curable.