Histoplasma Antigen Research Articles

Hypercalcemia Due to Disseminated Histoplasmosis in a Kidney Transplant Recipient with Negative Histoplasma Antigen Testing

Hypercalcemia Due to Disseminated Histoplasmosis in a Kidney Transplant Recipient with Negative Histoplasma Antigen Testing

Histoplasma capsulatum urinary antigen detection in a kidney transplant recipient with acute paracoccidioidomycosis: Case study and literature review.

Paracoccidioidomycosis (PCM) and histoplasmosis are endemic fungal diseases in South America. Both can lead to lung involvement with fungal dissemination progressing to systemic and severe clinical manifestations, especially in immunosuppressed hosts. As the population of immunosuppressed individuals has been rising, a higher occurrence of fungal infections is predicted in this setting. This poses challenges regarding the differential diagnosis due to overlapping clinical and laboratorial findings, hampering the management of cases. In this study, the authors discuss the occurrence of a false-positive Histoplasma urinary antigen detection in a kidney transplant recipient with acute PCM. Given the scarce information about this subject, a review on literature data is provided. A comprehensive literature search was conducted to investigate previous studies that found cross-reactivity between Histoplasma urinary antigen assays in human patients with confirmed diagnosis of PCM. Additionally, an update of PCM in transplant recipients is provided. The included studies reported 120 samples from patients with PCM tested for Histoplasma antigen, presenting an overall cross-reactivity of 51.67% and 17 cases of PCM in transplant recipients. CONCLUSIONS: The galactomannan urinary antigen developed to diagnose histoplasmosis can cross react with PCM, which may represent a concern in countries where both mycoses overlap.

Rapid CD4 cell count determination and Cryptococcus and Histoplasma antigen detection in people living with HIV: Implementation of a package of care strategy in a pilot study, Argentina

ObjectivesDespite advancements in HIV diagnosis and treatment, advanced HIV disease (AHD) is still a significant concern worldwide, especially in countries with a high percentage of undiagnosed cases and late-stage diagnoses. MethodsA prospective pilot study was conducted in Buenos Aires, Argentina to assess the feasibility of implementing a package for people living with HIV, integrating a point-of-care clusters of differentiation (CD4) test, followed by rapid Cryptococcus and Histoplasma antigen (Ag) detection. ResultsA total of 105 people living with HIV were enrolled, during June 2021 to October 2021. The VISITECT CD4 Advanced Disease Lateral Flow Assay (CD4-LFA) (Accubio) classified 98 (93%) patients with AHD. Compared with flow cytometry, the CD4-LFA performed with a high sensitivity (100%) but low specificity (19%) and limited accuracy (47%). In the 98 patients classified with AHD using the CD4-LFA, 16 tested positive for any of the rapid Ag used, including 12 patients positive for the Histoplasma Ag test and four positive for Cryptococcus Ag; all four patients with positive Cryptococcus Ag in sera and were diagnosed with meningitis. In the 30-day follow-up, one death was recorded. ConclusionsThe CD4-LFA correctly classified all patients with CD4 ≤200 cells/µL by flow cytometry, but a high frequency of patients misclassified with AHD was recorded. We also observed a high prevalence of opportunistic fungal infections, as previously observed in the hospital where this pilot study was conducted; however, in contrast with those previous reports, mortality was lower. The study underscores the importance of scaling up comprehensive care strategies and collaborating with governmental and non-governmental partners to enhance access to essential diagnostic tools and treatments for people living with HIV. Further research with larger sample sizes is needed to validate these findings.

Posaconazole followed by combination itraconazole and terbinafine for treatment of disseminated histoplasmosis in a cat.

This is the first reported use of posaconazole for the treatment of feline disseminated histoplasmosis. Approximately 1-year-old female spayed domestic longhair cat. The cat presented to our institution with weight loss, lymphadenomegaly, hepatosplenomegaly, limb edema, abdominal fluid distension and ulcerated cutaneous nodules. The cat had been previously diagnosed with disseminated histoplasmosis at another institution approximately 6 months prior. Clinical signs had been refractory to treatment with fluconazole. Itraconazole had next been tried, and the cat's weight continued to decline, lesions failed to regress, and the cat formed abdominal fluid distension and marked pelvic limb edema. The cat was prescribed posaconazole along with prednisolone. The cat's demeanor, body weight, and lesions all markedly improved. Histoplasma antigen was undetectable in urine samples while the cat was receiving posaconazole. However, posaconazole blood levels paired with markedly elevated ALT suggested potential toxicity and the drug was discontinued. Upon cessation of posaconazole, the cat's lesions returned with cytologic evidence of intralesional Histoplasma yeast. Itraconazole combine with terbinafine was prescribed. At last follow-up, the cat was clinically well, off all anti-fungal medication, and without detectable Histoplasma antigen in the urine. Posaconazole therapy showed promise in this case. Had a safe and therapeutic dose been arrived at, we suspect that posaconazole would have cleared or maintained clinical remission of this cat's disease. This is the first report using posaconazole and the first successful report using combination itraconazole and terbinafine for the treatment of feline disseminated histoplasmosis. Generic drugs were used throughout this case report; the drug manufacturers are unknown to the authors.

Hematuria Due to Possible Histoplasma-Associated Urinary Bladder Pseudotumor With Negative Serologic and Urine Antigen Testing

Abstract Histoplasma capsulatum is a ubiquitous dimorphic fungus causing multiple infectious syndromes, ranging from subclinical to severe disseminated disease. We present an unusual case of hematuria due to pedunculated urinary bladder mass in an immunocompetent host. Although the gold standard for diagnosis of histoplasmosis is through demonstration of characteristic yeast forms on histopathologic examination of infected tissue, or observation of typical mycelial growth in culture of clinical specimens, investigational multiplex polymerase chain reaction of formalinized tissue was helpful in this case due to conflicting serologic testing, equivocal morphologic findings on histopathologic examination and, surprisingly, a negative urine Histoplasma antigen despite anatomically proximal location within the urinary bladder. Although antigen immunoassay and serology are commonly used proxy diagnostics in Histoplasma-associated disease, varying performance characteristics in certain disease states, such as cases of locally proliferative infection mimicking neoplastic growth similar to this report, may lead to elusive diagnosis.

Screening with urine Histoplasma antigen test in asymptomatic patients starting TNF-alpha inhibitor therapy: a cohort study.

Histoplasmosis is the second most frequent granulomatous disease in patients treated with tumor necrosis factor (TNF)-α inhibitors, second only to tuberculosis. However, there is limited information about pre-therapy screening procedures and the need for preventive treatments for patients who will start immunobiologicals. This is a cohort study that evaluated the prevalence of histoplasmosis in asymptomatic HIV-negative patients before initiation of TNF-α inhibitors by testing for Histoplasma antigen in urine samples. The patients included completed a 180-day follow-up after the initiation of the biologics to assess the onset of symptoms suggestive of histoplasmosis. From January 2021 to December 2022, 54 patients who were prescribed a TNF-α inhibitor agent for treating autoimmune diseases in centers in southern Brazil were included. In the screening before therapy, the prevalence of a positive urinary Histoplasma antigen test was 14.8%. None of the 54 patients developed histoplasmosis after 6 months of immunobiological therapy, including the eight patients who tested positive. The prevalence of Histoplasma capsulatum infection in chronic patients may be higher than expected, but the impact of latent infection in asymptomatic patients is still uncertain, including those starting treatment with immunobiological drugs such as TNF-α inhibitors. Our study did not identify risk factors for the diagnosis of disseminated histoplasmosis in this group, including a positive result in an antigen test performed before immunobiological therapy. To date, there is no evidence to recommend routine antigen-based screening or preventive therapy for histoplasmosis before initiating a TNF-α inhibitor.

Detection of Histoplasma capsulatum and Blastomyces dermatitidis antigens in serum using a single quantitative enzyme immunoassay.

Histoplasma and Blastomyces antigen detection assays are commonly used diagnostic tools. However, a high level of cross-reactivity between these antigens prevents definitive pathogen identification by these assays alone. Retrospective analysis of 3,529 patients with Histoplasma and Blastomyces antigen testing performed on the same serum sample yielded an overall percent agreement of 99.3% (3,506 of 3,529; kappa: 0.859) between the two assays, suggesting that use of a single assay to detect both antigens may be an alternative diagnostic approach. We assessed performance of the Gotham BioTech Blastomyces antigen (GBA) enzyme immunoassay (EIA) (Portland, Maine) for detection of Blastomyces and Histoplasma antigens in serum. Comparison to the MiraVista Diagnostics Blastomyces (MVB) EIA showed 100% positive (24 of 24), negative (57 of 57), and overall (81 of 81) percent agreement. Additionally, 171 sera were used to compare the GBA EIA to the MiraVista Diagnostics Histoplasma (MVH) EIA, which showed 91.3% (63 of 69), 98% (100 of 102), and 95.3% (163 of 171) positive, negative, and overall percent agreement, respectively. Among eight patients with discordant GBA/MVH EIA results, seven had additional fungal testing performed, and results suggested that the MVH and GBA results were inaccurate for two and five samples, respectively. Overall, this study suggests that the GBA EIA has a high level of agreement with both of the commonly used, individual Blastomyces and Histoplasma antigen EIAs. By taking advantage of the high level of cross-reactivity between Blastomyces and Histoplasma antigen EIAs, utilization of a single antigen detection assay for these fungi provides an opportunity to optimize test utilization and decrease patient cost while maintaining a high level of diagnostic accuracy.

1506. Prevalence of Histoplasma Antigenuria among an outpatient Advanced HIV cohort in Kampala,Uganda

Abstract Background Histoplasmosis is a major cause of mortality in persons with advanced HIV disease (CD4< 200 cells/mcL) and areas of endemicity are evolving. Presenting symptoms of histoplasmosis may overlap with that of tuberculosis (TB). The true burden of histoplasmosis remains unknown in persons with advanced HIV disease, in part due to poor diagnostic capacity. We sought to evaluate the prevalence of Histoplasma antigenuria among outpatients with advanced HIV disease in Kampala, Uganda. Methods This prospective cohort study of outpatients with advanced HIV in Kampala, Uganda was nested within the ongoing ENCORE trial evaluating preemptive therapy and prophylaxis among outpatients with advanced HIV disease. Urine samples were obtained from participants at the time of enrollment and a Histoplasma galactomannan enzyme immunoassay (EIA) (Immy, Norman OK) was run on urine per manufacturer’s instructions. We obtained baseline characteristics and laboratory values, a statistical comparison by antigen status was not done due to a low number of positives. We calculated the prevalence of histoplasmosis in our cohort using EIA results. We obtained information on symptoms, TB diagnostics, and TB treatment for those with Histoplasma antigenuria. Results We tested 388 urine samples among participants with advanced HIV disease. Four samples were positive for Histoplasma antigen (1%). Baseline characteristics of participants are summarized in Table 1. Histoplasma antigen prevalence among participants with CD4< 100 cells/mcL was 2.5% (4/158). Of those that tested positive for histoplasmosis, the median CD4 count was 39 cells/mcL (interquartile range (IQR): 16–54), and median CRP was elevated at 29 (IQR 14-46). All four participants with Histoplasma antigenuria had a positive TB urine lipoarabinomannan (LAM, AlereLAM, Abbott, Palatine, IL, USA), though only two of four participants reported symptoms of cough, weight loss, and/or physical weakness. Three of four participants with positive Histoplasma antigen were started on anti-TB treatment. Patient symptoms resolved with no intervention. Conclusion Among outpatients with severe advanced HIV disease with CD4< 100 cells/mcL in Kampala, Uganda Histoplasma antigen prevalence was 2.5%. Disclosures All Authors: No reported disclosures

Histoplasma antigen detection in unconfirmed pulmonary tuberculosis and cross-reactivity with Aspergillus antigen in patients and in food in Jakarta, Indonesia.

H. capsulatum is endemic in Indonesia, but the value of Histoplasma antigen detection has not been studied. Histoplasma galactomannan (GM) ELISA was applied to sera of patients with unproven pulmonary tuberculosis (TB) and patients with a positive Aspergillus GM. Both Histoplasma and Aspergillus GM tests were performed to determine any possible cross-reaction with certain foods. Fourteen of 122 (11.5%) sera of patients with newly diagnosed clinical TB were positive for Histoplasma GM. The positivity rate in the serum of patients 5-6 and 12 months after TB diagnosis was 3.8% and 3.5%, respectively. Of 88 positive Aspergillus GM sera, 63 (71.6%) were also positive for Histoplasma GM. All tested foods were positive for Aspergillus GM, while 65% of foods were positive for Histoplasma GM. Galactomannan is widespread in sera and food in Jakarta, possibly related to food consumption. Histoplasma and Aspergillus antigen detection for the diagnosis will require additional means of confirming the diagnosis; negative tests may be more helpful for ruling out invasive histoplasmosis and aspergillosis.

An unexpected cause of refractory thrombocytopenia in post renal transplant patient

Post renal transplant patient often present with cytopenias including thrombocytopenia, this could be multifactorial including the immunosuppressive drugs, viral infections. Patient need immediate supportive treatment. The underlying etiology needs to be identified and treated. One of the less suspected cause is opportunistic infection like disseminated histoplasmosis. Progressive disseminated histoplasmosis is an uncommon opportunistic infection, largely affecting immunocompromised individuals, among organ transplant patients most commonly occur in post kidney transplant and patients on calcinurin inhibitor. The initial manifestation are fever, weight loss, hepatosplenomegaly, thrombocytopenia to an acute, rapidly fatal course causing resp. failure, shock, coagulopathy and multiorgan failure. Diagnosis can we made by histoplasma antigen assay or demonstration of histoplasma among tissue and bone marrow biopsy. Treatment include Intravenous amphotericin B with Long term itraconazole. We present an interesting case of disseminated histoplasmosis in post renal transplant patient presented with rashes, bleeding manifestation and severe thrombocytopenia, interestingly thrombocytopenia

Cost-effectiveness evaluation of routine histoplasmosis screening among people living with advanced HIV disease in Latin America and the Caribbean.

Histoplasma antigen can be detected in people with advanced HIV disease (AHD), allowing for early and accurate diagnosis of histoplasmosis. The aim of this analysis was to assess the cost-effectiveness of routine histoplasmosis screening using antigen detection, among people with AHD. We developed a decision analytic model to evaluate Histoplasma antigen screening among people with AHD. The model estimated the costs, effectiveness, and cost-effectiveness of routine screening for Histoplasma antigen compared to the current practice of no routine Histoplasma antigen screening. The model includes stratification by symptoms of histoplasmosis, severity of presentation, and estimates of 30-day mortality. Data sources were taken from the Pan American Health Organization (PAHO) Strategic Fund databases on public purchases of medicines, and published literature on treatment outcomes. Outcome measures are life years saved (LYS), costs (US dollars), and incremental cost-effectiveness ratios (ICERs). Routine Histoplasma antigen screening avoids an estimated 17% of deaths in persons with advanced HIV disease, and is cost-effective compared to no histoplasmosis screening, with an ICER of $26/LYS. In sensitivity analysis assuming treatment for histoplasmosis with liposomal amphotericin, Histoplasma antigen screening remains cost-effective with an ICER of $607/LYS. Histoplasma antigen screening among people with AHD is a cost-effective strategy and could potentially avert 17% of AIDS-related deaths. Prospective evaluation of histoplasmosis screening is warranted to determine effectiveness and treatment outcomes with this strategy.

Prevalence of Histoplasma Antigenuria among Outpatient Cohort with Advanced HIV in Kampala, Uganda.

In sub-Saharan Africa, an estimated 25% of people with HIV present with advanced HIV and are at high risk of opportunistic infections. Whereas histoplasmosis has occasionally been seen in Uganda, the understanding of the local risk of acute infection is limited. We sought to determine the prevalence of Histoplasma antigenuria using an enzyme immunoassay (EIA, clarus Histoplasma GM EIA, IMMY; Norman, OK, USA) in a cohort of outpatients with advanced HIV disease in Kampala, Uganda. Among the persons with positive urine Histoplasma antigen tests, we assessed their clinical presentation and outcomes. The EIA was run on stored urine samples as per the manufacturer's instructions. Specimens ≥1 EIA units were considered positive. Among the 388 tested urine samples, 4 (1.2%) were positive for Histoplasma antigen. The histoplasmosis prevalence among participants with a CD4 < 100 cells/mcL was 2.5% (4/158). Three of the four participants with a positive Histoplasma antigen test reported systemic symptoms consistent with histoplasmosis. All four participants had a positive urine lipoarabinomannan test and were treated for tuberculosis. By the four-week follow-up visit, all participants were clinically improved, alive, and in care without antifungal therapy. In advanced HIV, the clinical presentations of tuberculosis and histoplasmosis overlap. The value of histoplasmosis screening and pre-emptive treatment is an area of future research.

Evaluation of an enzyme immunoassay and immunodiffusion for detection of anti-Histoplasma antibodies in serum from cats and dogs.

Histoplasma antigen and anti-Histoplasma antibody detection are used to support the diagnosis of histoplasmosis. There is a paucity of published data on antibody assays. Our primary hypothesis was that anti-Histoplasma immunoglobulin G (IgG) antibody detection using enzyme immunoassay (EIA) will be more sensitive as compared to immunodiffusion (ID). Thirty-seven cats and 22 dogs with proven or probable histoplasmosis; 157 negative control animals. Residual stored sera were tested for anti-Histoplasma antibodies using EIA and ID. Results of urine antigen EIA were reviewed retrospectively. Diagnostic sensitivity was calculated for all three assays and compared between immunoglobulin G (IgG) EIA and ID. The diagnostic sensitivity of urine antigen EIA and IgG EIA, interpreted in parallel, was reported. Sensitivity of IgG EIA was 30/37 (81.1%; 95% confidence interval [CI], 68.5%-93.4%) in cats and 17/22 (77.3%; 95% CI, 59.8%-94.8%) in dogs. Diagnostic sensitivity of ID was 0/37 (0%; 95% CI, 0%-9.5%) in cats and 3/22 (13.6%; 95% CI, 0%-28.0%) in dogs. Immunoglobulin G EIA was positive in all animals (2 cats and 2 dogs) with histoplasmosis but without detectable antigen in urine. Diagnostic specificity of IgG EIA was 18/19 (94.7%; 95% CI, 74.0%-99.9%) in cats and 128/138 (92.8%; 95% CI, 87.1%-96.5%) in dogs. Antibody detection by EIA can be used to support the diagnosis of histoplasmosis in cats and dogs. Immunodiffusion has an unacceptably low diagnostic sensitivity and is not recommended.

The incidence of histoplasmosis and cryptococcal antigenemia among patients attending a large HIV clinic in Trinidad

Our aim was to determine the incidence disseminated histoplasmosis and cryptococcal antigenemia among 280 patients with a CD4<350 cells/mm3 attending a large HIV clinic in Trinidad over the period November 2021-June 2022. Sera were screened for cryptococcal antigen (CrAg) using the Immy CrAg Immunoassay (EIA) and the Immy CrAg lateral flow assay (LFA). Urine was screened for Histoplasma antigen using the Immy EIA and the Optimum Imaging Diagnostics (OIDx) LFA. For the purposes of analysis, it was assumed, that all patients with positive urine Histoplasma antigen tests by both EIA and LFA and those with a single positive urine Histoplasma antigen test and clinical features of disseminated histoplasmosis were true positives. The incidence of probable disseminated histoplasmosis and cryptococcal antigenemia were 6.4% (18/280) and 2.5% (7/280) respectively. The sensitivity and specificity of the Immy Histoplasma EIA were 100% (95% CI, 81.5%-100%) and 98.5% (95% CI, 96.1% - 99.6%) respectively as compared to the OIDx Histoplasma LFA of 88.9% (95% CI, 65.3% - 98.6%) and 93.9% (95% CI, 90.3% - 96.5%) respectively, with substantial agreement between the 2 test kits (Kappa value = 0.763; 95% CI 0.685, 0.841). Testing for disseminated histoplasmosis in HIV patients is important in endemic areas.

Optimization of a commercial Histoplasma galactomannan EIA test in a population from an endemic area of histoplasmosis in southern Brazil.

Since 2020 the World Health Organization (WHO) recommends Histoplasma antigen detection for the diagnosis of disseminated histoplasmosis (DH) in people living with HIV (PLHIV). Here we aimed to optimise the IMMY's Clarus® Histoplasma GM enzyme immunoassay (EIA), evaluating the best cut-off in the semi-quantitative (SQ-HGM EIA), also known as 'calibrator cut-off procedure'. The optimization was done using the quantitative standard procedure (Q-HGM EIA), also known as 'standard curve procedure', as reference test. A retrospective study from an endemic area of DH in southern Brazil was carried out including 264 patients investigated for DH using the test. Receiver Operator Characteristic curve was plotted, and sensitivity and specificity of the SQ-HGM EIA were calculated. The study included 24 positive (values ≥ 0.20 ng/ml) and 240 negative patients by the Q-HGM EIA. According to the manufacturer SQ-HGM EIA protocol, the new SQ-HGM EIA cut-off of 0.8 EIA units was validated, resulting in sensitivity and specificity of 88% and 98.7%, respectively. Our study pioneers and brings important data about the optimization of the Histoplasma antigen testing for the diagnosis of DH in a population from Southern Brazil. This optimization also reduced the amount of reagents used, lowering the cost associated with testing.

914: SEPSIS IN THE STREAM: SEVERE LEGIONELLA AND HISTOPLASMA PNEUMONIA ACQUIRED FROM SPRING WATER

Introduction: Legionnaires’ disease (LD) and pulmonary histoplasmosis are important causes of community-acquired pneumonia (CAP). Both infections are acquired via inhalation from a myriad of reported contaminated environmental sources. Herein, we present a case of concurrent LD and pulmonary histoplasmosis ultimately linked to contaminated spring water used in a home continuous positive airway pressure (CPAP) device, highlighting the importance of source identification and proper patient education on device maintenance. Description: A 67-year-old male with obstructive sleep apnea (OSA) was admitted to our ICU for acute respiratory distress syndrome (ARDS) requiring endotracheal intubation after one week of dyspnea associated with fevers, vomiting, and diarrhea. Vital signs on arrival were significant for fever of 102.8°F, vasopressor-dependent hypotension, and refractory hypoxemia despite maximal ventilator support. Thoracic CT revealed bilateral multifocal consolidations and urine legionella antigen test was positive, confirming the diagnosis of LD. He was also diagnosed with possible pulmonary histoplasmosis after serum histoplasma antigen resulted positive. Treatment included salvage ARDS supportive measures and broad-spectrum antimicrobials, including levofloxacin and amphotericin B. His ICU course was complicated by a prolonged ventilator wean requiring tracheostomy. Upon further questioning, the patient’s family revealed he used a nearby spring as his primary water source, including in his home CPAP device. He ultimately transitioned to a step-down unit with plans for outpatient pulmonary follow-up on discharge. Discussion: Legionella pneumonia and pulmonary histoplasmosis both represent significant and potentially fatal causes of CAP. Environmental reservoirs remain the primary source of infection and may persist since investigations are often reserved for large outbreaks. Our case highlights a source of both legionella and histoplasmosis not previously reported. It demonstrates the value of taking a thorough history while recognizing non-traditional sources of both infections. It also highlights the importance of emphasizing proper device maintenance. Increased awareness of risk factors for these infections enables earlier diagnosis and treatment and ideally improves outcomes.

613. Novel use of Ritonavir boosting to achieve therapeutic itraconazole levels in disseminated Histoplasmosis

Abstract Background Itraconazole is a poorly soluble antifungal drug with variable pharmacokinetics. Serum levels vary between patients and over time, due to absorption issues and drug-drug interactions. Itraconazole suspension has more predictable absorption than capsules, but is poorly tolerated. Newer formulations dispersing drug in polymer aim to improve bioavailability, but are costly and not widely available. Standard therapy for histoplasmosis is induction with liposomal amphotericin B (LAmB) followed by 12+ months of itraconazole therapy with target pre-dose levels of 1-4 mg/L. Methods A 33yo M presented with weight loss, fever and dyspnoea, having returned to the UK from Nicaragua. He had been taking adalimumab for Crohn’s disease, quiescent for years following a prior small bowel resection. Empiric antifungal therapy with LAmB was commmenced, prior to confirmation of disseminated histoplasmosis by urinary antigen and blood culture. His course was complicated by significant bowel inflammation, requiring subtotal colectomy and end-ileostomy. Since surgery, he has had a high output stoma, with rapid transit time and reduced absorption. Results Despite itraconazole dose titration to 300mg TDS, levels were generally &amp;lt; 0.5 mg/L and maximum serum itraconazole level achieved was 0.64 mg/L. The patient was trained with a view to self-OPAT LAmB. On day 117 of antifungal therapy, ritonavir 100mg once daily was added. Four days after this, itraconazole level was 1.39 mg/L (from 0.34 mg/L) and maintained target concentration even after a switch from itraconazole suspension to capsules (Fig.1) with significant fungal marker response (Fig. 2). Figure 1.Itraconazole dosing and levels pre- and post-ritonavir Total daily itraconazole dose (suspension followed by capsules) was mapped over time. There is a period where LAmB alone was used surrounding the colorectal surgery. Serum itraconazole levels dramatically increased 2 days after the introduction of ritonavir 100mg once daily and remained above target trough even after switching to itraconazole capsules. Figure 2.Fungal marker (B-D-glucan and Histoplasma urinary Ag) response to antifungal therapy The response of serum beta-D-glucan and quantitative urinary Histoplasma antigen EIA (Miravista Labs) is represented alongside concurrent antifungal therapy. Of note, the first four urinary Histoplasma Ag levels were reporte as above the limit of detection (&amp;gt; 20 ng/mL) and are represented here as an arbitrary value of 25 ng/mL. Conclusion Use of ritonavir alone to boost itraconazole has not previously been described. It avoids the longer-term complications of intravenous access and adverse renal and other effects of LAmB. Itraconazole is both a substrate and inhibitor of cytochrome P450 3A4 (CYP3A4) and inhibits P-glycoprotein, resulting in considerable drug:drug interactions. Ritonavir is a more potent inhibitor of CYP3A4. Use of ritonavir-boosted itraconazole amounted to a 99% reduction in cost vs LAmB over 6 months. It may offer a reliable and cost-effective method of boosting itraconazole where other drug:drug interactions do not preclude its use. Disclosures All Authors: No reported disclosures.

900: A REPORT OF DISSEMINATED HISTOPLASMOSIS IN AN IMMUNOCOMPROMISED PATIENT FOLLOWING COVID-19 INFECTION

Introduction: Histoplasmosis results from spore inhalation of Histoplasma capsulatum, an endemic fungus in the soil of the Ohio and Mississippi River Valleys of the United States. While the majority of infections with H. capsulatum are asymptomatic and self-limited, immunosuppressed patients may develop severe, disseminated disease. Few reports have described disseminated histoplasmosis following SARS-CoV-2 (COVID-19) infection such as described in this case. Description: A 69-year-old female was evaluated for shortness of breath. Her medical history was significant for rheumatoid arthritis on methotrexate and recent COVID-19 infection treated with dexamethasone. Initial CT-angiography of the chest showed patchy bilateral ground glass opacities. She had leukopenia with white blood cell count of 1.3 K/uL and elevated procalcitonin of 5.88 ng/mL. Broad spectrum empiric antibiotics were initiated. On day 6, the patient decompensated and required ICU transfer. Urine histoplasma antigen, M and H precipitin bands, and serum galactomannan antigen returned positive. Amphotericin B was initiated. The patient underwent bronchoscopy with bronchoalveolar lavage showing atypical reactive macrophages with rare intracellular organisms suspicious for fungi. Repeat CT of the chest, abdomen, and pelvis showed extensive bilateral ground glass opacities, bilateral pulmonary calcifications consistent with granulomas, and calcifications in the spleen and liver. On hospital day 10, the patient required intubation due to hypoxemic respiratory failure. Despite appropriate antifungal therapy, she had worsening encephalopathy, leukocytosis, erythema nodosum, and renal failure. She passed away on day 19. Discussion: This case highlights the development of disseminated histoplasmosis in an immunocompromised adult following COVID-19 infection. It was not until treatment with high dose glucocorticoids that the patient developed disseminated disease and declined. It is important to be aware of the impact that the COVID-19 pandemic has on the emergence of infectious disease and the role its treatment plays in immune suppression. Disseminated histoplasmosis is a consideration for immunocompromised patients in high risk, H. capsulatum endemic areas who are being treated for COVID-19 with high doses of steroids for prolonged periods.

Comparison of Indirect Fungal Diagnostic Tests in Patients With Proven Histoplasmosis.

Histoplasmosis is a common cause of invasive fungal infection in endemic regions and accurate diagnosis is difficult without direct tissue culture or pathology. Indirect fungal antigen testing for various fungal pathogens are typically performed to assist with diagnostic workup, though cross-reaction can lead to difficulty in interpreting results. We aimed to compare indirect fungal diagnostic tests and evaluate prevalence of positive antigen testing for non-Histoplasma fungal pathogens in patients with proven histoplasmosis. We performed a single-center retrospective review of adult patients with proven histoplasmosis diagnosed by fungal culture and/or cytology from January 2010 to March 2018. Patient demographics, clinical characteristics, and results of fungal antigen testing for Histoplasma, Blastomyces, Aspergillus, Cryptococcus, and (1→3)-β-D-glucan were evaluated. Two different urine Histoplasma antigen assays were used during the study period. Fifty-seven of 182 (31.3%) patients reviewed had proven histoplasmosis and presented with acute pulmonary (n = 10), chronic pulmonary (n = 7), and disseminated (n = 40) disease. Forty-one (72%) of these patients were immunosuppressed. Urine Blastomyces antigen (93%) and serum (1→3)-β-D-glucan (88%) were commonly positive in patients with histoplasmosis, whereas Aspergillus antigen was detected in 50% of patients and Cryptococcus antigenemia was rare (5%). In patients with disseminated disease, the MiraVista urine Histoplasma antigen assay had higher sensitivity than the Viracor urine Histoplasma antigen assay (86% vs 50%, respectively; P = .019). Noninvasive fungal antigen assays are helpful diagnostic tools; however, given their low specificity, clinicians must be aware of the various clinical presentations of invasive fungal infections and be aware of the limitations of these tests.

Prevalence of Histoplasmosis among Persons with Advanced HIV Disease, Nigeria.

We sought to determine the prevalence of probable disseminated histoplasmosis among advanced HIV disease (AHD) patients in Nigeria. We conducted a cross-sectional study in 10 sites across 5 of 6 geopolitical zones in Nigeria. We identified patients with urinary samples containing CD4 cell counts <200 cells/mm3 or World Health Organization stage 3 or 4 disease who also had >2 clinical features of disseminated histoplasmosis, and we tested them for Histoplasma antigen using a Histoplasma enzyme immune assay. Of 988 participants we recruited, 76 (7.7%) were antigen-positive. The 76 Histoplasma antigen-positive participants had significantly lower (p = 0.03) CD4 counts; 9 (11.8%) were also co-infected with tuberculosis. Most antigen-positive participants (50/76; 65.8%; p = 0.015) had previously received antiretroviral treatment; 26/76 (34.2%) had not. Because histoplasmosis is often a hidden disease among AHD patients in Nigeria, Histoplasma antigen testing should be required in the AHD package of care.