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ABSTRACTHistoplasmosis is an endemic mycosis in North America frequently reported along the Ohio and Mississippi River Valleys, although autochthonous cases occur in non-endemic areas. In the United States, the disease is provoked by two genetically distinct clades of Histoplasma capsulatum sensu lato, Histoplasma mississippiense (Nam1) and H. ohiense (Nam2). To bridge the molecular epidemiological gap, we genotyped 93 Histoplasma isolates (62 novel genomes) including clinical, environmental, and veterinarian samples from a broader geographical range by whole-genome sequencing, followed by evolutionary and species niche modelling analyses. We show that histoplasmosis is caused by two major lineages, H. ohiense and H. mississippiense; with sporadic cases caused by H. suramericanum in California and Texas. While H. ohiense is prevalent in eastern states, H. mississipiense was found to be prevalent in the central and western portions of the United States, but also geographically overlapping in some areas suggesting that these species might co-occur. Species Niche Modelling revealed that H. ohiense thrives in places with warmer and drier conditions, while H. mississippiense is endemic to areas with cooler temperatures and more precipitation. In addition, we predicted multiple areas of secondary contact zones where the two species co-occur, potentially facilitating gene exchange and hybridization. This study provides the most comprehensive understanding of the genomic epidemiology of histoplasmosis in the USA and lays a blueprint for the study of invasive fungal diseases.

BACKGROUND: Invasive fungal disease caused by dimorphic fungi is associated with significant morbidity and mortality. Super-bioavailability itraconazole (SUBA-itra) is a novel antifungal agent with pharmacokinetic advantages over currently available formulations. In this prospective comparative study, we report the outcomes of patients with endemic fungal infections (histoplasmosis, blastomycosis, coccidioidomycosis, and sporotrichosis). METHODS: This open-label randomized trial evaluated the efficacy, safety, and pharmacokinetics SUBA-itra compared with conventional itraconazole (c-itra) treatment for endemic fungal infections. An independent data review committee determined responses on treatment days 42 and 180. RESULTS: Eighty-eight patients were enrolled for IFD (SUBA-itra, n = 42; c-itra, n = 46) caused by Histoplasma (n = 51), Blastomyces (n = 18), Coccidioides (n = 13), or Sporothrix (n = 6). On day 42, clinical success was observed with SUBA-itra and c-itra on day 42 (in 69% and 67%, respectively, and on day 180 (in 60% and 65%). Patients treated with SUBA-itra exhibited less drug-level variability at days 7 (P = .03) and 14 (P = .06) of randomized treatment. The concentrations of itraconazole and hydroxyitraconazole were comparable between the 2 medications (P = .77 and P = .80, respectively). There was a trend for fewer adverse events (AEs; 74% vs 87%, respectively; P = .18) and serious AEs (10% vs 26%; P = .06) in the SUBA-itra-treated patients than in those receiving c-itra. Serious treatment-emergent AEs were less common in SUBA-itra-treated patients (12% vs 50%, respectively; P < .001). CONCLUSIONS: SUBA-itra was bioequivalent, well tolerated, and efficacious in treating endemic fungi, with a more favorable safety profile than c-itra. CLINICAL TRIALS REGISTRATION: NCT03572049.

Background: Auranofin is an approved anti-rheumatic drug that has a broad-range inhibitory action against several microorganisms, including human pathogenic fungi. The auranofin activity against Histoplasma capsulatum, the dimorphic fungus that causes histoplasmosis, has not been properly addressed. Since there are few therapeutic options for this life-threatening systemic mycosis, this study evaluated the effects of auranofin on H. capsulatum growth and expression of virulence factors. Methodology/principal findings: Minimal inhibitory and fungicidal concentrations (MIC and MFC, respectively) of auranofin against 15 H. capsulatum strains with distinct genetic backgrounds were determined using the yeast form of the fungus and a microdilution protocol. Auranofin activity was also assessed on a macrophage model of infection and on a Tenebrio molitor invertebrate animal model. Expression of virulence-related genes was compared between auranofin treated and untreated H. capsulatum yeast cells using a quantitative PCR assay. Auranofin affected the growth of different strains of H. capsulatum, with MIC and MFC values ranging from 1.25 to 5.0 μM and from 2.5 to >10 μM, respectively. Auranofin was able to kill intracellular H. capsulatum yeast cells and conferred protection against the fungus in the experimental animal model of infection. Moreover, the expression of catalase A, HSP70, superoxide dismutase, thioredoxin reductase, serine proteinase, cytochrome C peroxidase, histone 2B, formamidase, metallopeptidase, Y20 and YPS3 proteins were reduced after six hours of auranofin treatment. CONCLUSIONS/SIGNIFICANCE: Auranofin is fungicidal against H. capsulatum and reduces the expression of several virulence-related genes, which makes this anti-rheumatic drug a good candidate for new medicines against histoplasmosis. Author summary: Histoplasmosis is a serious disease caused by the fungus Histoplasma capsulatum, which can be life-threatening and has limited treatment options. In this study, we investigated the potential of auranofin, a drug originally approved for treating rheumatoid arthritis, to combat H. capsulatum. We tested auranofin against different strains of the fungus and found that it effectively inhibited fungal growth. This drug was also effective in killing the fungus within cells from the immune system and provided protection in an experimental animal model. Furthermore, auranofin reduced the expression of several genes associated with the fungus's ability to cause disease. These genes are involved in critical functions such as detoxifying harmful substances and maintaining cellular structures. By suppressing these genes, auranofin hampers the fungus's ability to survive and cause infection. These findings suggest that auranofin could be repurposed as a treatment for histoplasmosis, offering a new avenue for therapy against this challenging infection. This research is significant because it highlights the potential of existing drugs to treat other diseases, broadening our arsenal of available treatments and contributing to better healthcare solutions. [ABSTRACT FROM AUTHOR]

The Caribbean continues to have high HIV prevalence globally with concurrently high mortality rates due to opportunistic Infections. This study addresses the prevalence of histoplasmosis and cryptococcosis among patients living with advanced HIV disease (AHD) in Trinidad and Tobago, focusing on the implementation of antigen-based diagnostic assays. Conducted as a cross-sectional survey across five HIV treatment sites, 199 participants with advanced HIV disease were enrolled between July 2022 and September 2023. Diagnostic testing was performed using the Clarus Histoplasma Galactomannan Enzyme Immunoassay (EIA), and the Immy CrAg® LFA Cryptococcal Antigen Lateral Flow Assay on urine and blood samples, respectively. Results revealed that 14.6% of participants were found to be co-infected with either histoplasmosis or cryptococcosis, with histoplasmosis being more prevalent (10.5%) than cryptococcosis (4.0%). The study found no significant demographic differences between newly diagnosed and previously diagnosed participants. However, a lower median CD4 count was associated with a higher risk of fungal opportunistic infections. The findings underscore the critical role of systematic use of fungal antigen-based diagnostic assays among patients with AHD to improve the timely diagnosis and treatment of fungal infections among people living with HIV in resource-limited settings and to improve patient outcomes and survival. [ABSTRACT FROM AUTHOR]

Background Progressive disseminated histoplasmosis is a significant issue in Latin America, particularly in Brazil, contributing to high mortality rates. Objectives Our objectives were to comprehensively describe histoplasmosis treatment with various amphotericin B (AmB) formulations, including mortality rates, adverse effects and risk factors for mortality. Methods This multicentre retrospective cohort study (January 2014–December 2019) evaluated medical records of patients with proven or probable histoplasmosis treated with at least two doses of AmB in seven tertiary medical centres in Brazil. We assessed risk factors associated with death during hospitalization using univariate and multivariate analyses. Results The study included 215 patients, mostly male (n  = 158, 73%) with HIV infection (n  = 187, 87%), and a median age of 40 years. Only 11 (5%) patients initiated treatment with liposomal amphotericin B (L-AmB). Amphotericin B deoxycholate (D-AmB) was administered to 159 (74%) patients without changes in the treatment. The overall mortality during hospitalization was 23% (50/215). Variables independently associated with mortality were use of D-AmB (OR 4.93) and hospitalization in ICU (OR 9.46). There was a high incidence of anaemia (n  = 19, 90%), acute kidney injury (n  = 96, 59%), hypokalaemia (n  = 73, 55%) and infusion reactions (n  = 44, 20%) during treatment. Conclusions We found that D-AmB was the main formulation, which was also associated with a higher mortality rate. Lipid formulations of AmB have become more readily available in the public health system in Brazil. Further studies to evaluate the effectiveness of L-AmB will likely show improvements in the treatment outcomes for patients with disseminated histoplasmosis. [ABSTRACT FROM AUTHOR]

Histoplasma capsulatum (H. capsulatum) is considered to be one of the most extensively spread dysmorphic fungi worldwide. Histoplasmosis primarily impacts patients with weakened immune systems and can result in a diverse range of clinical manifestations. In immunocompetent patients, the disease may manifest as a self-limiting or asymptomatic infection; however, in immunocompromised individuals, it can occur as a debilitating, disseminated disease. Diagnosing histoplasmosis may be challenging. A medical professional that specializes in treating endemic fungal illnesses is better able to assist with an accurate and timely diagnosis since they have a deeper grasp of these illnesses. Consequently, the process of diagnosing histoplasmosis might be difficult for less experienced physicians. The case presented is an example of the myriad faces that histoplasmosis can take on, mimicking other common infectious or malignant conditions, leading to extensive work-up and invasive procedures in establishing the diagnosis of this otherwise benign condition. We hereby report the case of disseminated histoplasmosis in a young immunocompetent female patient. [ABSTRACT FROM AUTHOR]

Granulomatous lesions, though rare, can affect diverse body regions, including the larynx, presenting diagnostic challenges. In India, where malignancy and tuberculosis prevail, fungal infections are often overlooked. We present a case of 34 year old male with complaint of change in voice which was approached as malignancy but later turned out to be histoplasmosis on histopathology. Diagnostic challenges arise due to symptoms overlapping with other conditions. Our case underscores the importance of considering fungal etiologies in endemic regions, especially when symptoms persist despite treatment. [ABSTRACT FROM AUTHOR]

Zoonotic diseases are caused by viruses, bacteria, fungi and parasites and they comprise about 75% of all emerging infectious diseases. These can be transmitted via the direct (scratches on skin or animal bites) or indirect mode (through environmental shedding of infectious agent by the infected animal) of transmission. Environmental changes, whether in the form of urbanization, industrialization or destruction of wildlife habitats, lead to more human invasion in wildlife areas, subsequently leading to an increased passage of animals towards human dwellings and more exposure to animals, making humans susceptible to these infections. Climate change is another major factor. Global warming and the evolving thermotolerance of fungi, adapting more to human body temperature than their saprophytic nature, is leading to the emergence of humans as new hosts for fungi. The domestication of animals, rising populations, enhanced tourism, migratory populations, intrusions into wildlife, etc., are other known factors. Zoonotic fungal infections have long been neglected and are now gaining due attention. In this review, we briefly discuss the various aspects currently known for zoonotic fungal infections and bring forth the importance of this particular issue to be addressed in a timely manner. [ABSTRACT FROM AUTHOR]

Human endemic mycoses are potentially fatal diseases caused by a diverse group of fungi that can alter their morphology in response to an increase in temperature. These thermally dimorphic fungi affect both healthy and immunocompromised hosts, causing a substantial health and economic burden. Despite this, the diagnosis of endemic mycoses is still a formidable challenge for several reasons, including similar symptomatology, limited utility of classical diagnostic methods, inaccessibility to reliable molecular approaches in most endemic areas, and a lack of clinical suspicion out of these regions. This review summarizes essential knowledge on thermally dimorphic fungi and the life-threatening diseases they cause. The principle, advantages and limitations of the methods traditionally used for their diagnosis are also described, along with the application status and future directions for the development of alternative diagnostic strategies, which could help to reduce the disease burden in endemic areas. [ABSTRACT FROM AUTHOR]

To explore associations between histoplasmosis and race and ethnicity, socioeconomic status, and rurality, we conducted an in-depth analysis of social determinants of health and histoplasmosis in 8 US states. Using the Minority Health Social Vulnerability Index (MH SVI), we analyzed county-level histoplasmosis incidence (cases/100,000 population) from the 8 states by applying generalized linear mixed hurdle models. We found that histoplasmosis incidence was higher in counties with limited healthcare infrastructure and access as measured by the MH SVI and in more rural counties. Other social determinants of health measured by the MH SVI tool either were not significantly or were inconsistently associated with histoplasmosis incidence. Increased awareness of histoplasmosis, more accessible diagnostic tests, and investment in rural health services could address histoplasmosis-related health disparities.

Disseminated histoplasmosis is a rare yet serious fungal infection that primarily affects individuals with compromised immune systems. While it is widely known for its endemicity in the Midwest region of the USA, recent studies have indicated a noteworthy increase in sporadic cases, suggesting a widening of the endemic region for the pathology. This report describes a case of disseminated histoplasmosis in a 39-year-old female with a history of lupus, hypertension, anxiety, asthma, idiopathic edema, and fibromyalgia from a nonendemic region, who presented with cyclic fevers of unknown origin, peripheral edema, and oral sores. On admission, she was diagnosed with acute pyelonephritis and started on levofloxacin. She continued to develop worsening leukopenia and thrombocytopenia in addition to bone and joint pain. Bone marrow biopsy results were consistent with hemophagocytic lymphohistiocytosis (HLH) triggered by histoplasmosis confirmed by PCR. Despite an initial negative urine antigen test for Histoplasma, subsequent tests showed rising levels. The patient's clinical course was marked by a protracted hospital stay, multiple systems involvement, severe de-conditioning, drug side effects requiring adjustments in anti-fungal medications, and interdisciplinary care. The patient gradually improved and was discharged home with follow-ups. This study underscores the role of timely diagnosis of disseminated histoplasmosis in patients with underlying autoimmune diseases for favorable outcomes, thereby emphasizing the necessity of heightened clinical suspicion. By addressing the nuanced challenges that arise in managing multiple complications in the domain of disseminated histoplasmosis, advocates a comprehensive interdisciplinary approach to optimize patient care.

Histoplasmosis is a fungal disease associated with substantial mortality rates among persons with advanced HIV disease. Our systematic review synthesized data on the global prevalence of Histoplasma­-caused antigenuria in persons with HIV. We searched PubMed/Medline, Embase, and Scopus databases on January 3, 2023, to identify cross-sectional and cohort studies evaluating Histoplasma antigenuria prevalence among adults with HIV infection. We calculated point estimates and 95% CIs to summarize prevalence. Of 1,294 studies screened, we included 15. We found Histoplasma antigenuria among 581/5,096 (11%; 95% CI 11%–12%) persons with HIV and 483/3,789 persons with advanced HIV disease (13%; 95% CI 12%–14%). Among persons with HIV and symptoms consistent with histoplasmosis, Histoplasma antigenuria prevalence was 14% (95% CI 13%–15%; 502/3,631 participants). We determined that persons with advanced HIV disease, inpatients, and symptomatic persons might benefit from a systematic approach to early detection of histoplasmosis using urine antigen testing.

Introduction. Histoplasmosis is not an endemic form of fungal infection in Russia; its sporadic cases are mainly associated with the import of the fungus from endemic countries. We consider it necessary to demonstrate a rare case of the disseminated histoplasmosis development in a kidney transplant recipient.Objective. Demonstration of a case of the disseminated histoplasmosis development in a kidney transplant recipient.Results. The clinical manifestations of the disease were described; the affected organs were macroscopically and histologically studied, which made it possible to diagnose disseminated histoplasmosis.Conclusions. This case prompts being on alert to potential occurrence of fungal infections, including non-endemic ones, in patients receiving immunosuppressive therapy.

Introduction: The aetiologies in unilateral and bilateral adrenal lesions can be different with different clinical implications and management guidelines, the latter having aetiologies like hyperplasia, infections, infiltrative lesions and neoplasia. Bilateral tumours are more likely to have hereditary/syndromic associations. There is limited data on the clinical and pathological profile of bilateral adrenal lesions. Methods: This was a retrospective study where patients with bilateral adrenal lesions were selected from a total of 266 patients with adrenal lesions who presented to our institute between January 2016 and August 2022. The demographic, laboratory and imaging data were retrieved from the Hospital Information System and patient case files. Results: The study included 51 patients; the mean age at presentation was 51.15 years (range 14 to 82 years). Forty-eight patients (94.1%) were symptomatic at presentation with an average duration of symptoms being 10.68 months (range 10 days to 1 year). The most common presentation was adrenal insufficiency in 18 cases (38%), followed by fever in 17 cases (36%). The commonest aetiology, as revealed on histopathology, was histoplasmosis (n = 22, 43%), followed by pheochromocytoma (n = 11, 21.5%), metastases (n = 6, 11.7%), adrenal hyperplasia (n = 5, 9.8%), adrenocortical adenoma (n = 1, 1.9%), lymphoma (n = 3, 5.8%), neuroblastoma (n = 1, 1.9%), myelolipoma (n = 1, 1.9%) and tuberculosis (n = 1, 1.9%). Histoplasmosis and metastatic lesions were commonly seen in older people, and pheochromocytoma was associated with young age. 6/11 patients with a diagnosis of bilateral pheochromocytoma were associated with family history, genetic mutation and extra-adrenal involvement. Conclusion: The approach to bilateral adrenal lesions differs from that of unilateral lesions due to differences in aetiologies and the more significant role of genetics in some bilateral tumours. The age at presentation, presenting symptoms, lesion size and biochemical features help delineate varied underlying aetiologies.

Background: 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. Objectives: 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. Methods: 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. Findings: 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. Author summary: Paracoccidioidomycosis (PCM) and histoplasmosis are severe fungal diseases occurring simultaneously in South America. They can cause similar clinical manifestations, especially in immunosuppressed hosts. This poses challenges regarding the differential diagnosis due to overlapping clinical and laboratorial findings, hampering the management of individual cases. In this study, the authors report the occurrence of a false-positive urinary test to detect histoplasmosis in a kidney transplant recipient with acute PCM. Given the scarce information about this subject, a review on literature data is provided. As conclusion, this study highlights the urinary test developed to diagnose histoplasmosis can cross react with PCM, which may represent a concern in countries where both mycoses overlap. [ABSTRACT FROM AUTHOR]

This document is a reference list and author contributions for a case report titled "Gingival ulcer in a patient with psoriatic arthritis." The case involved a 70-year-old woman with psoriatic arthritis who developed a symptomatic gingival ulcer while being treated with methotrexate and risedronate sodium. An incisional biopsy was performed, and the diagnosis was determined to be Epstein-Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU). The ulcer resolved after 30 days of follow-up, and tooth #27 was extracted due to extreme mobility after the biopsy. The authors have no conflicts of interest to disclose and the patient provided written informed consent for publication. [Extracted from the article]

Background Blastomycosis, coccidioidomycosis, and histoplasmosis are environmentally acquired fungal diseases that clinically resemble bacterial and viral community-acquired pneumonia and require laboratory testing for diagnosis. Patients frequently present to primary care and experience diagnostic delays when a fungal etiology is not initially suspected. Current national-level public health surveillance for these diseases is limited and does not include laboratory data, so nationwide testing practices are unknown. Methods We identified laboratory tests for blastomycosis, coccidioidomycosis, and histoplasmosis ordered during 1 March 2019–29 February 2024 and performed within a major national commercial laboratory system. We analyzed test results, patient and healthcare provider features, reasons for testing, and temporal trends. Results Results included 5693 Blastomyces complement fixation tests (of those, 12% were positive), 71 858 immunodiffusion tests (0.1% positive), and 1186 serum enzyme immunoassay (EIA) tests (11% positive); 154 989 Coccidioides EIA immunoglobulin M results (5% positive) and 154 968 immunoglobulin G results (8% positive); and 46 346 Histoplasma complement fixation tests (30% positive), 49 062 immunodiffusion tests (1% positive), 35 506 serum EIA tests (4% positive), and 82 489 urine EIA tests (2% positive). Most histoplasmosis (58%–74%) and blastomycosis (42%–68%) tests were ordered from hospitals, whereas coccidioidomycosis tests were most frequently ordered by primary care providers (40%). A yearly average of 2727 positive tests were ordered by healthcare providers in states without public health surveillance for these diseases. Conclusions Blastomycosis, coccidioidomycosis, and histoplasmosis are likely underdetected in primary care settings or by public health surveillance. Increased testing by primary care providers and expanded surveillance are needed to reduce disease burden. [ABSTRACT FROM AUTHOR]

In Indonesia, 2.4% of all new tuberculosis patients had multi-drug resistant disease (MDR-TB); an estimated 24,000 incidences. Historical case series of MDR-TB described a high frequency of cavitation and poor prognosis. The diagnosis of chronic pulmonary aspergillosis (CPA) relies on raised levels of Aspergillus IgG antibodies, and detectable Histoplasma IgG antibodies are suspicious for chronic pulmonary histoplasmosis (CPH). We investigated whether MDR-TB patients might have concurrent CPH or CPA. This was a cross-sectional study with 50 MDR-TB patients. ELISA was used to detect Histoplasma IgG antibodies and lateral flow assay was used to detect Aspergillus IgG/IgM antibodies. Several other possible disease determinants were assessed by multivariate analysis. Of the 50 MDR-TB patients, 14 (28%) and 16 (32%) had positive Histoplasma or Aspergillus serology; six patients (12%) had dual antibody reactivity. Radiological abnormalities in positive patients included diffuse or local infiltrates, nodules, consolidation, and apical cavities, consistent with CPH and CPA. Patients with detectable fungal antibodies tended to have worse disease, and 4 of 26 (15.3%) died in the first 5 months of dual infection (p = 0.11 compared with no deaths in those with only MDR-TB). The criteria for the diagnosis of CPH and CPA were fulfilled in those with moderately and far advanced disease (13 of 14 or 93%) and 12 of 16 (75%), respectively. Damp housing was the only determinant associated with Histoplasma antibodies (PR 2.01; 95%CI 0.56–7.19), while pets were associated with the Aspergillus antibody (PR 18.024; 95%CI 1.594–203.744). CPA or CPH are probably frequent in MDR-TB patients in Indonesia and may carry a worse prognosis. [ABSTRACT FROM AUTHOR]

Histoplasmosis is a fungal disease associated with substantial mortality rates among persons with advanced HIV disease. Our systematic review synthesized data on the global prevalence of Histoplasma-caused antigenuria in persons with HIV. We searched PubMed/Medline, Embase, and Scopus databases on January 3, 2023, to identify cross-sectional and cohort studies evaluating Histoplasma antigenuria prevalence among adults with HIV infection. We calculated point estimates and 95% CIs to summarize prevalence. Of 1,294 studies screened, we included 15. We found Histoplasma antigenuria among 581/5,096 (11%; 95% CI 11%-12%) persons with HIV and 483/3,789 persons with advanced HIV disease (13%; 95% CI 12%-14%). Among persons with HIV and symptoms consistent with histoplasmosis, Histoplasma antigenuria prevalence was 14% (95% CI 13%-15%; 502/3,631 participants). We determined that persons with advanced HIV disease, inpatients, and symptomatic persons might benefit from a systematic approach to early detection of histoplasmosis using urine antigen testing. [ABSTRACT FROM AUTHOR]

Central nervous system histoplasmosis is a serious complication of a common endemic mycosis, but it is rare in immunocompetent hosts. SARS-CoV-2 has introduced significant challenges into the healthcare setting with overlapping clinical presentations that may delay the diagnosis of alternative conditions. Additionally, it may lead to immune dysregulation and increase the risk for secondary infections, including invasive fungal diseases. Limited reports have described disseminated histoplasmosis in adults associated with COVID-19, but none have described central nervous system infection or complications in pediatric patients. We report a case of disseminated histoplasmosis involving the central nervous system in a previously healthy 13-year-old male with SARS-CoV-2 infection. An extensive immunological evaluation did not identify an underlying immunodeficiency. We highlight the potential of COVID-19 immune dys-regulation to contribute to the development or progression of invasive fungal disease. [Pediatr Ann. 2024;53(8):e305–e309.] [ABSTRACT FROM AUTHOR]

Histoplasma capsulatum (var. capsulatum Hcc and duboisii Hcd), is a dimorphic fungus that causes histoplasmosis. It usually affects people coming from endemic areas, causing a variety of clinical manifestations up to progressive disseminated histoplasmosis (PDH), especially among people living with HIV (PLWH). We conducted a systematic review to assess histoplasmosis burden of PLWH in Europe. The review follows PRISMA guidelines, with protocol registered in PROSPERO (CRD42023429779). Seventy-eight articles were selected, including 109 patients (32 women). On overall, median age was 37  years. Forty-six patients were Americans, 39 Africans, 17 Europeans, 5 Asians, in 2 cases nationality was not specified. Cases were mainly diagnosed in Italy (28.4%), France (17.3%) and Spain (17.4%), with a north–south gradient. Six cases lacked epidemiologic links with endemic areas. Concerning CDC HIV staging at diagnosis, the information was available for 60 PLWH (55%) and all subjects were at stage C3 except for two subjects at stage B3. PDH was the AIDS-presenting illness in 39 patients. Most patients had a PDH (80.7%); other common extrapulmonary forms were isolated cutaneous histoplasmosis (7.3%), or lymphatic localization (2.7%). In 30 cases, the diagnosis was made by analyzing only one sample. For the remaining 79 cases, multiple samples were collected from each patient. Regarding the biological sample more frequently used for the diagnosis of histoplasmosis, bronchoalveolar lavage sample was taken from 39 patients, and tested positive in 51.3% of cases; 36 patients underwent a skin biopsy which was positive in 86.1% of cases and 28 patients performed bone-marrow biopsy, which led to the diagnosis of histoplasmosis in 92.9% of cases. The identification of Histoplasma capsulatum was available in 97 PLWH through examination of different samples: Hcc and Hcd were identified in 89 and 8 PLWH, respectively. Concerning therapies, 67.9% were treated with liposomal amphotericin B, 18.3% with itraconazole, 10 died pre-treatment. The overall mortality rate was 23.6%. Non-survivors exhibited more frequently gastrointestinal symptoms (p  =  0.017), while cutaneous signs correlated with better survival (p  =  0.05). Untreated patients faced higher mortality (p  <  0.001). Histoplasmosis should be considered amongst opportunistic infection in PLWH, even in Europe, especially if patients originate from or have travelled to endemic areas. [ABSTRACT FROM AUTHOR]

Background Hemophagocytic lymphohistiocytosis (HLH) is considered a rare disease with high morbidity and mortality risks. Most research on this disease is conducted in pediatric settings. Therefore, this study aimed to describe the clinical characteristics, laboratory findings, and outcomes related to HLH in people living with human immunodeficiency virus (HIV)/AIDS) and disseminated histoplasmosis. Methods A retrospective and descriptive study was conducted in a tertiary hospital in México City from January 2018 to December 2022, including people living with HIV who had disseminated histoplasmosis confirmed through direct microbiological or immunological methods with an HScore ≥169 or who met 5 of the 8 HLH-2004 criteria. Results HLH occurred in 36.1% (n = 26) of patients with HIV and disseminated histoplasmosis; the majority were men (84.9%), and their mean age (standard deviation) was 30.19 (5.6) years. The most frequent clinical manifestations were hepatomegaly (100%), fever (96.2%), and dyspnea (84.6%). The most common biochemical changes were hyperferritinemia (100%), elevated lactate dehydrogenase (100%), and bicytopenia (61.5%). Partial thromboplastin time (P =.012) and prothrombin time (P =.004) were associated with the 30-day mortality rate, and the 30-day survival rate was 65.4%. Conclusions We detected a high frequency of HLH; therefore, we encourage physicians to use diagnostic prediction tools (HLH-2004 and HScore criteria) in each reassessment for timely detection. [ABSTRACT FROM AUTHOR]

Immunosuppressed patients can present with opportunistic infections resulting from an intrinsic systemic disease, which easily evolves into more aggressive and less common conditions. This work reports a clinical case of a female patient with histoplasmosis lesions in the nasal and oral mucosa, including pulmonary, hematological, and hepatic impairment, which led to the diagnosis of HIV seropositivity. In the presence of severe immunosuppression, morbidity is increased due to deep fungal infections and their unusual clinical characteristics can make diagnosis difficult. Therefore, it can be very helpful to recognize these clinical characteristics in order to determine early diagnostic interventions. It is important to recognize mucocutaneous manifestations of histoplasmosis because the biopsy of these lesions, and subsequent histopathological analysis, is one of the quickest, safest, and cheapest methods of diagnosis. [ABSTRACT FROM AUTHOR]

The second international meeting on endemic mycoses of the Americas (IMEMA) and the first international symposium on implantation mycoses (ISIM) took place in Santiago del Estero, Argentina, on September 25–27, 2023. The conference provided a platform for researchers, clinicians, and experts to discuss the latest developments in the field of endemic and implantation mycoses. Topics included epidemiology, diagnostic advances, treatment strategies, and the impact of environmental factors on the spread of these fungal diseases. IMEMA and ISIM contributed to the regional discourse on the mycoses, emphasizing the importance of international cooperation in addressing these public health challenges. [ABSTRACT FROM AUTHOR]

Differently from immunocompromised patients, very little information is available in the literature regarding the clinical presentation, epidemiology, and outcomes of histoplasmosis in non-immunosuppressed individuals living in endemic areas. This retrospective case series study was carried out by reviewing the medical records of non-immunocompromised patients with histoplasmosis, residents in a hyperendemic area in northeastern Brazil, between 2011 and 2022. Thirty HIV-negative patients were identified with histoplasmosis, and 19 cases met the inclusion criteria: three had acute, five subacute and one chronic pulmonary forms; two with mediastinal picture and eight had disseminated disease (two with severe symptoms). The median age of our sample was 32.7 years old [interquartile range: 24–45]. Most of the patients were male (male-to-female ratio = 15:4) and resided in the state capital (n  = 9). The majority had a previous history of exposure to well-known risk factors for Histoplasma infection. Pulmonary nodules were observed in all subacute form, two patients (acute and subacute forms) were initially treated empirically for pulmonary tuberculosis; one death was registered in the subacute form. The chronic pulmonary form of histoplasmosis was diagnosed in one patient only after the symptoms persisted despite specific treatment. The primary clinical manifestations of the moderate form of DH were enlarged lymph nodes, with histopathology being the main diagnostic method. The cases were detected as isolated occurrences and not as an outbreak, suggesting that exposure to Histoplasma can be more widespread than presumed. Despite the self-limiting nature of the disease, death can occur even in previously heathy patients. [ABSTRACT FROM AUTHOR]

Antigen testing is an important diagnostic tool for histoplasmosis but has limited availability globally. We evaluated the OIDx urine lateral flow antigen assay among 204 persons suspected to have histoplasmosis. Among patients with proven histoplasmosis, sensitivity was 33.3% (3/9, 95% CI 7.5%–70.1%) and specificity 80.5% (157/195, 95% CI 74.3%–85.8%). The MiraVista urine antigen test had better specificity (96.9%) and equal sensitivity. The OIDx test demonstrated 33.3% (3/9) positive agreement and 84.0% (163/194) negative agreement with the MiraVista test. These results should be considered in the context of our low HIV prevalence population with a mixture of pulmonary and disseminated disease. [ABSTRACT FROM AUTHOR]

Histoplasmosis is a frequent cause of infections in people living with HIV/AIDS (PLWHA). This study introduces the application of a Histoplasma capsulatum urine antigen lateral flow assay (LFA) for diagnosing disseminated histoplasmosis in PLWHA in Suriname. The LFA's diagnostic accuracy was compared with the current diagnostic approach, aiming to assess whether this test resulted in improved early detection and management. Additionally, the prevalence of histoplasmosis among advanced stage HIV patients without clinical suspicion of infection was evaluated using the same LFA. In total, 98 patients were included in the study, of which 58 were classified as "possible disseminated histoplasmosis (DH)" based on clinical criteria and 40 as 'controls". Of these possible DH cases, only 19 (32.7%) had a positive LFA. During the study, decisions for treatment were made without the treating physician being aware of the LFA result. Only 55% of the patients who started treatment for histoplasmosis based on clinical criteria had a positive LFA, and 21% of untreated patients had a positive LFA. This study shows that combining clinical signs with LFA results enhances diagnostic accuracy and is cost effective, resulting in better treatment decisions. Author summary: People living with HIV in Suriname often present to care in a late stage of their infection. A common infection in these patients is Disseminated Histoplasmosis (DH). This is caused by a fungus, Histoplasma capsulatum. DH is currently difficult to diagnose. This study evaluated the use of a urine test for the diagnosis of DH, called LFA, in patients with advanced-stage HIV-infection. In the study, 98 advanced-stage HIV infected patients were included. Of these, 58 had signs and symptoms that could be attributable to DH. The other 40 patients were not suspected of DH. In all these patients the usual workup was done. The urine histoplasmosis LFA was carried out afterwards, so the result did not influence clinical decisions. We compared the clinical diagnoses of all patients to the results of the LFA. The results show that only 55% of the patients with a clinical diagnosis of DH and who started antifungal treatment had a positive LFA. Of the untreated patients 21% had a positive LFA. We conclude that treatment decisions solely based on clinical signs and symptoms lead to both over- and undertreatment and that adding this test to the clinical workup of patients suspected of DH, is cost-effective. [ABSTRACT FROM AUTHOR]

Coccidioidomycosis, histoplasmosis, and blastomycosis are underrecognized and frequently misdiagnosed fungal infections that can clinically resemble bacterial and viral community-acquired pneumonia. This guidance is intended to help outpatient clinicians test for these fungal diseases in patients with community-acquired pneumonia to reduce misdiagnoses, unnecessary antibacterial use, and poor outcomes. [ABSTRACT FROM AUTHOR]

Objective: Rare disease Background: Histoplasma capsulatum is prevalent in the mid-eastern United States and is an environmental fungus that causes human infection by the inhalation of its spores. It is commonly associated with areas containing large amounts of bird excrement and can survive for years in the soil. Only 1% of infected individuals develop disseminated histoplasmosis or Histoplasma endocarditis. Case Report: A 61-year-old man with atrial fibrillation had 8 months of fatigue, low-grade fevers, night sweats, and unexplained weight loss presented to the Emergency Department. He worked and lived in Central Florida and although he raised cattle, he denied exposure to birds or bats with regularity. A transesophageal echocardiogram confirmed a sessile echo density on the atrial surface of the mitral valve. His microbial Karius cell-free DNA test from his blood sample was positive for Histoplasma capsulatum, and he was immediately given intravenous liposomal amphotericin for 2 weeks. A tissue valve was used to successfully replace his mitral valve along with a coronary artery bypass and a maze procedure for his persistent atrial fibrillation and atrial futter. The diagnosis of mitral valve endocarditis from disseminated histoplasmosis was confirmed by pathological analysis, and he was sent home on long-term itraconazole maintenance treatment. Conclusions: Surgical intervention in combination with anti-fungal medication can be a lifesaving intervention for disseminated histoplasmosis. A thorough history is particularly important when evaluating a patient with an unknown infectious source, especially assessing for risk factors, including exposure to environmental factors, workplace, and animals. [ABSTRACT FROM AUTHOR]

Background: Histoplasmosis is caused by Histoplasma capsulatum which can lead to a broad spectrum of disease. Culture remains the gold standard till date; however, this is a slow-growing fungus that may take a considerable time before a conclusion can be made. This case highlights the importance of careful bone marrow evaluation to identify the fungal bodies, especially in the presence of increased hemophagocytic activity. Case Presentation: We present a 36-year-old man with newly diagnosed retroviral disease, presented with fever, pancytopenia, and hepatosplenomegaly. Bone marrow aspirate smear showed increased hemophagocytic activity with the presence of intracellular organisms. Trephine biopsy showed similar features with the presence of fungal bodies detected via Periodic acid-Schiff stain. Conclusion: In conclusion, bone marrow examination plays a crucial role in the diagnosis of some fungal infections, especially in centers where culture or serological tests are not readily available. [ABSTRACT FROM AUTHOR]

Histoplasma capsulatum is a dimorphic fungi endemic to the Ohio and Mississippi River valleys. Immunocompetent persons who become infected are generally asymptomatic or present with mild symptoms. Symptomatic disease is seen primarily in immunocompromised patients with pulmonary manifestations being the most common presentation. We present a case of a young HIV-negative male who required 4 exploratory laparotomies over the course of 4 months during 2 hospitalizations due to discrete perforations of the ileum and jejunum caused by biopsy-proven gastrointestinal histoplasmosis despite maximal medical therapy as well as a gastric perforation. [ABSTRACT FROM AUTHOR]

(1) Background: Only a few studies on histoplasmosis in immunocompetent patients have been reported in French Guiana. Therefore, we conducted a detailed clinical description of hospitalized patients suffering with histoplasmosis among non-HIV patients. (2) Methods: This is a single-center, retrospective study conducted at Cayenne Hospital Center between 2008 and 2022. (3) Results: Our cohort was composed of 31 (91%) adults (>18 years of age) and 3 (9%) children, with a sex ratio, M:F, of 1:2. The median age was higher among the women than among the men (70 versus 54 years). The collection of respiratory samples constituted the majority of the performed examinations (38%). Fever (>37 °C) was found in 56% of patients. Surprisingly, the histoplasmosis was disseminated in 82% of patients with an overall case fatality rate of 14.7%. However, immunosuppressive conditions were found in 52% (16/31) of the adult patients, including lymphoid hemopathies, diabetes and immunosuppressive drugs. Conclusions: This disease, though rare and usually considered a mostly benign disease in non-HIV patients, presented a relatively high mortality rate in our cohort. Thus, histoplasmosis should be suspected, screened and investigated as a first line of defense in highly endemic areas, even in immunocompetent and non-HIV patients, especially those with fever or chronic respiratory symptoms. [ABSTRACT FROM AUTHOR]

Histoplasmosis is an endemic and invasive mycosis caused by Histoplasma capsulatum. We conducted a retrospective study comparing immunosuppressed patients without human immunodeficiency virus (HIV) with a historical cohort of people with HIV and histoplasmosis. We included 199 patients with proven or probable histoplasmosis, of which 25.1% were people without HIV. Diabetes mellitus, chronic kidney disease, hematologic neoplasms, rheumatologic diseases, and transplantations were more frequent among people without HIV (P <.01). Forty-four percent of immunocompromised patients without HIV died within the first 6-week period following their diagnosis. A high suspicion index for histoplasmosis should be kept in immunosuppressed patients. [ABSTRACT FROM AUTHOR]

Histoplasmosis is a global infection caused by the thermally dimorphic fungus, Histoplasma capsulatum complex. It is endemic in the United States, as well as in Central and South America. In Taiwan, histoplasmosis is rare, with the first reported case not occurring until 1977. We summarized a total of 17 cases reported in Taiwan over the past 40 years and provided detailed descriptions for four probable indigenous cases. Due to the lack of rapid diagnostic tools and clinical suspicion, histoplasmosis may be underdiagnosed in Taiwan. We recognize that a limitation of our review is the lack of data on the environmental surveillance for H. capsulatum complex in Taiwan. Conducting a further phylogenetic analysis on both environmental and clinical isolates would provide valuable evidence for the region. [ABSTRACT FROM AUTHOR]

Background: Fever of unknown origin (FUO) is a diagnostic challenge with highly heterogeneous causes. Its etiology can change according to the studied regions, and the chance of reaching a diagnosis depends on available resources. The aim of this study is to describe the clinical characteristics, etiology and the usefulness of diagnostic aids in cases of FUO managed over 12 years in a Colombian reference center. Methodology: Single-institution retrospective case series. All cases of FUO between 2006 and 2017 were identified with the help of an electronic medical record search software. Cases of adults with fever for more than three weeks who remained undiagnosed after three days of hospitalization are described. Results: Of 1,009 cases evaluated, 112 cases met the inclusion criteria (median age 43 years, 66% men). The etiologies identified were infectious (31.2%), inflammatory (20.5%), neoplastic (14.3%), and miscellaneous (2.7%) diseases. 31.2% remained without etiological diagnosis. The most frequent conditions were tuberculosis (17%), Hodgkin's lymphoma (7.1%), systemic lupus erythematosus (6.3%), disseminated histoplasmosis, and adult Still's disease. Contrast tomography and biopsies were the studies that most frequently supported or confirmed the final diagnosis. Conclusions: This series of contemporary Latin American cases suggests that the categories of FUO etiologies are similar to those reported in studies from developed countries, with tuberculosis being the most frequent cause in our setting. Our results highlight the importance of tomography-guided invasive studies in the diagnostic approach to FUO. [ABSTRACT FROM AUTHOR]

Histoplasmosis is an expected endemic mycosis in solid organ transplant recipients and occurs as a primary infection, reactivation, or, rarely, acquired from an infected allograft. Reactivation is favored by maintenance immunosuppression or anti‐rejection therapy, which facilitates the appearance of disseminated forms as well as unusual presentations. We present the case of a 66‐year‐old woman with isolated tenosynovitis due to Histoplasma capsulatum 25 years after a kidney transplant. [ABSTRACT FROM AUTHOR]

Background: A splenic artery pseudoaneurysm is a rare pathology that occurs mainly secondary to pancreatitis, abdominal trauma, peptic ulcers, pancreatic and gastric cancers, and infections. It is best diagnosed using computed tomography angiography and typically treated using endovascular embolization and, in some cases, open or laparoscopic surgery. In this report, we present a case of a ruptured mycotic splenic artery pseudoaneurysm containing Histoplasma capsulatum, which to our knowledge is the first case to report a mycotic splenic artery pseudoaneurysm of this nature. Case presentation: We report a case of a 42-year-old white male with past medical history of Hepatitis C and IV drug abuse who presented to the Emergency Department with a 24-h history of severe diffuse abdominal pain. He was tachycardic and peritonitic on exam. Work-up demonstrated leukocytosis and lactic acidosis. Computed tomography of the abdomen and pelvis with intravenous contrast showed hemoperitoneum and active extravasation of contrast from the splenic artery into the splenic hilum, associated with a surrounding hematoma measuring 5.3 × 5.0 cm, concerning for ruptured splenic artery pseudoaneurysm. The patient was taken emergently for exploratory laparotomy, where a large intraperitoneal hematoma was evacuated. A ruptured splenic artery pseudoaneurysm was identified, isolated, and controlled, followed by completion splenectomy. Final pathology demonstrated a 3.0 × 1.3 × 0.3 cm pseudoaneurysm wall and a 14 × 9.5 × 5.5 cm spleen containing multiple necrotizing granulomata positive for the presence of Histoplasmosis species. The patient recovered appropriately and was discharged on post-operative day five. Conclusions: This case demonstrates a successful approach to a ruptured mycotic splenic artery pseudoaneurysm resulting in a positive outcome. It is a unique case as it highlights, to our knowledge, the first report of splenic artery aneurysm secondary to Histoplasma capsulatum infection. This report helps further the understanding of the pathophysiology as well as the natural history of mycotic splenic pseudoaneurysms. [ABSTRACT FROM AUTHOR]

Background In Latin America, tuberculosis (TB) and histoplasmosis are two of the most frequent opportunistic infections affecting people living with human immunodeficiency virus (HIV). However, there are limited data on the clinical characteristics and outcomes of patients with concurrent TB and histoplasmosis infections. Methods This was a retrospective observational study to describe the clinical, epidemiological and laboratory characteristics and outcomes of 21 patients living with HIV (PLHIV) who were diagnosed with concurrent histoplasmosis and TB between 2017 and 2021 in Guatemala City, Guatemala. Results Most patients were male and were newly diagnosed with HIV. All patients had advanced HIV disease (AHD). They presented with a median CD4 count of 20 cells/µl. The most common symptoms reported by the patients were fever, weight loss, cough and diarrhoea. Twelve patients died within 6 months of baseline evaluation, for a mortality rate of 57.1%. Conclusions PLHIV with concurrent TB and histoplasmosis infections are characterised by AHD, predominantly presenting with disseminated forms of these infections and with unspecific symptoms and signs. This evidence calls for early HIV and opportunistic infection screening and insights into the challenges and opportunities for the efficient diagnostic and therapeutic management of patients with AHD with concurrent histoplasmosis and TB infections. [ABSTRACT FROM AUTHOR]

Postmortem studies show gastrointestinal tract involvement in as many as 70% of patients affected by disseminated histoplasmosis. Although gastrointestinal involvement is common in disseminated disease, the presentation of small intestinal perforation is exceedingly rare with few reported cases in the literature. Herein we present our institutional case series. The aim of the study is to describe small intestinal perforation in gastrointestinal histoplasmosis with attention to management and outcomes. This is a retrospective single-institution review of patients ≥ 18 years of age treated for small intestinal perforation due to gastrointestinal histoplasmosis. A prospectively maintained institutional database was searched from 2002 to 2022. Data obtained included demographics, comorbidities, treatment course, and outcomes. Five patients with a mean age of 54 years (range 25–72) were identified. Pertinent underlying comorbid conditions included Crohn's disease, psoriatic arthritis, rheumatoid arthritis, and solid organ transplantation. All patients were on chronic immunosuppressive medication(s) with the most common being tumor necrosis factors alpha inhibitors and corticosteroids. Four had a clinical diagnosis of perforation based on physical examination and imaging. All patients underwent segmental resection(s) of the small intestine and received medical treatment with intravenous amphotericin B and eventual transition to an oral antifungal. No patients experienced complications related to surgery. The limitations of the study include nonrandomized retrospective review, single-institution experience, and small patient sample size. Although rare, histoplasmosis should be considered in the differential of patients on chronic immunosuppressive therapy who present with gastrointestinal symptoms concerning perforation, especially from endemic areas. Small intestinal perforation due to gastrointestinal histoplasmosis can be successfully treated with resection and antifungal therapy. [ABSTRACT FROM AUTHOR]

Histoplasmosis, a significant mycosis primarily prevalent in Africa, North and South America, with emerging reports globally, poses notable health challenges, particularly in immunocompromised individuals such as people living with HIV/AIDS and organ transplant recipients. This systematic review, aimed at informing the World Health Organization's Fungal Priority Pathogens List, critically examines literature from 2011 to 2021 using PubMed and Web of Science, focusing on the incidence, mortality, morbidity, antifungal resistance, preventability, and distribution of Histoplasma. We also found a high prevalence (22%–44%) in people living with HIV, with mortality rates ranging from 21% to 53%. Despite limited data, the prevalence of histoplasmosis seems stable, with lower estimates in Europe. Complications such as central nervous system disease, pulmonary issues, and lymphoedema due to granuloma or sclerosis are noted, though their burden remains uncertain. Antifungal susceptibility varies, particularly against fluconazole (MIC: ≥32 mg/l) and caspofungin (MICs: 4–32 mg/l), while resistance to amphotericin B (MIC: 0.125–0.16 mg/l), itraconazole (MICs: 0.004–0.125 mg/l), and voriconazole (MICs: 0.004–0.125 mg/l) remains low. This review identifies critical knowledge gaps, underlining the need for robust, globally representative surveillance systems to better understand and combat this fungal threat. [ABSTRACT FROM AUTHOR]

A 9-month-old female intact toy poodle and a 1-year-old female intact Labrador retriever mix presented to separate teaching hospitals for chronic histories of malaise and clinicopathologic evidence of hepatic dysfunction. The signalment and clinical histories of these dogs prompted consideration of a congenital portosystemic shunt as a primary differential. However, microscopic evaluation of peritoneal effusion, pleural effusion, and peripheral blood samples from the dogs revealed round to ovoid yeast organisms morphologically most compatible with Histoplasma capsulatum. Additional testing confirmed histoplasmosis in each case. The poodle underwent a computed tomography (CT) study, which showed hepatomegaly with a spleno-gonadal shunt, pancreatic and gastric wall edema, and marked peritoneal effusion, findings compatible with portal hypertension and secondary acquired shunt formation. The dog was later humanely euthanized due to clinical deterioration, and on necropsy hepatic histoplasmosis was verified, with additional affected tissues comprising lungs and spleen. The Labrador Retriever mix responded clinically and clinicopathologically to antifungal therapy, though no abdominal imaging was performed to definitively exclude the possibility of a congenital portosystemic shunt. In retrospect, several features were more compatible with histoplasmosis than portosystemic shunt in these cases, including hyperbilirubinemia, effusion, and hepatomegaly. These findings serve as a reminder of the need to interpret serum biochemical findings in the context of the totality of the clinicopathologic data and imaging findings, as well as the diagnostic value of microscopy in the evaluation of hematologic and body cavity fluid samples. [ABSTRACT FROM AUTHOR]

Review of histoplasmosis and blastomycosis antigen testing for 39 patients hospitalized with these diseases found that there were significantly longer turnaround times between the time of specimen collection and receipt of positive test results among those patients who had worse outcomes. [ABSTRACT FROM AUTHOR]