Management of disseminated histoplasmosis in a high-complexity clinic in Cali, Colombia.

Histoplasmosis presents a substantial clinical challenge globally, with a particular prevalence in South America, especially among patients with concurrent Human Immunodeficiency Virus (HIV) infection. Despite itraconazole's established efficacy, investigating alternative therapeutic approaches remains imperative. This is the largest study in our region to date, assessing the effectiveness of the less explored posaconazole treatment. This observational study, conducted at Fundación Valle del Lili (FVL) from 2016 to 2022, encompassed adults with disseminated histoplasmosis. Patients (n = 31) were treated with liposomal amphotericin B as an initial treatment, followed by consolidation treatment with posaconazole or itraconazole. Patients with single-organ cases, those lacking microbiological diagnosis, those who received initial treatment with antifungals other than liposomal Amphotericin B and those with < 6 months follow-up were excluded (Figure 1). Analyses considered population characteristics, treatments, and outcomes. Patients (average age: 45.6; 58.1% female) had common comorbidities (HIV 38.7%, solid organ transplantation 29% and oncologic disease 12.9%). Lungs (48.4%) and lymph nodes (16.1%) were commonly affected. Biopsy (64.5%) was the primary diagnostic method. Initial treatment with liposomal amphotericin B (100%) was given for 14 days on average. Follow-up indicated 71% completion with 19.4% requiring treatment modifications. Notably, 70.9% completed a posaconazole consolidation regimen over 350 days on average. Drug interactions during consolidation (80.6%) were common. No relapses occurred, and three deaths unrelated to histoplasmosis were reported. Traditionally, itraconazole has been the prevalent initial treatment; however, in our cohort, 55.9% of patients received posaconazole as the primary option. Encouragingly, posaconazole showed favorable tolerance and infection resolution, suggesting its potential as an effective and well-tolerated alternative for consolidation treatment. This finding prompts further exploration of posaconazole, potentially leading to more effective patient care and better outcomes.

Histoplasmosis is a critical concern in South America, notably among human immunodeficiency virus patients, leading to high mortality rates. This study, the largest in our region, investigates the effectiveness of posaconazole as an alternative treatment to itraconazole. The results offer the potential for enhanced patient care and improved outcomes.

Histoplasmosis peritonitis in an immunocompetent patient: case report.

Histoplasmosis is a fungal infection most frequently seen in immunocompromised patients. It is endemic in Central and South America and in Africa. The infection is usually asymptomatic in a healthy individual. Extrapulmonary dissemination can be seen in immunocompromised hosts. Gastrointestinal manifestations frequently involve the terminal ileum and cecum, mimicking Crohn's disease or malignancy. We describe the case of a 36-year-old healthy man from Cameroon, living in Switzerland for 13 years and without any medical nor surgical history, who presented peritonitis not responding to antibiotics. CT-scan showed bowel obstruction and signs of peritonitis. We opted for an explorative laparoscopy, which was converted to laparotomy with extensive adhesiolysis. Diagnostic of histoplasmosis was confirmed by histology and PCR analysis on biopsy. To our knowledge, this is the first described case of peritonitis as main outcome of a disseminated histoplasmosis involving the peritoneum in an immunocompetent patient.

Single High Dose of Liposomal Amphotericin B in Human Immunodeficiency Virus/AIDS-Related Disseminated Histoplasmosis: A Randomized Trial.

BACKGROUND: Histoplasmosis is a major AIDS-defining illness in Latin America. Liposomal amphotericin B (L-AmB) is the drug of choice for treatment, but access is restricted due to the high drug and hospitalization costs of the conventional long regimens. METHODS: Prospective randomized multicenter open-label trial of 1- or 2-dose induction therapy with L-AmB versus control for disseminated histoplasmosis in AIDS, followed by oral itraconazole therapy. We randomized subjects to: (i) single dose 10 mg/kg of L-AmB; (ii) 10 mg/kg of L-AmB on D1, and 5 mg/kg of L-AmB on D3; (iii) 3 mg/kg of L-AmB daily for 2 weeks (control). The primary outcome was clinical response (resolution of fever and signs/symptoms attributable to histoplasmosis) at day 14. RESULTS: A total of 118 subjects were randomized, and median CD4+ counts, and clinical presentations were similar between arms. Infusion-related toxicity, kidney toxicity at multiple time-points, and frequency of anemia, hypokalemia, hypomagnesemia, and liver toxicity were similar. Day 14 clinical response was 84% for single-dose L-AmB, 69% 2-dose L-AmB, and 74% for control arm (P = .69). Overall survival on D14 was 89.0% (34/38) for single-dose L-AmB, 78.0% (29/37) for 2-dose L-AmB, and 92.1% (35/38) for control arm (P = .82). CONCLUSIONS: One day induction therapy with 10 mg/kg of L-AmB in AIDS-related histoplasmosis was safe. Although clinical response may be non-inferior to standard L-AmB therapy, a confirmatory phase III clinical trial is needed. A single induction dose would markedly reduce drug-acquisition costs (>4-fold) and markedly shorten and simplify treatment, which are key points in terms of increased access.

Progressive disseminated histoplasmosis: The experience in one non-endemic medical center.

Histoplasmosis, the most common endemic mycosis in North America, presents in a myriad of ways, spanning the spectrum from self-limiting pneumonia to progressive disseminated histoplasmosis (PDH). Toward better describing contemporary histoplasmosis syndromes, risks, and outcomes, this single-center retrospective cohort study was performed (2009-2019). The population who developed PDH was similar to that with other forms of histoplasmosis (OFH) except for higher rates of preexisting immunocompromising conditions (91.3% vs. 40%, P < .001) and a trend toward receiving more chronic immunosuppression (65.2% vs. 33.3%, P = .054) compared to those with OFH. Diagnosis was most frequently achieved by urinary or serum antigen positivity. People with PDH more frequently tested positive compared to those with OFH, but negative tests did not rule out histoplasmosis. Median time to diagnosis was prolonged among people with both PDH and OFH (32 vs. 31 days, respectively). Following diagnosis, people with PDH received more liposomal amphotericin (78.3% vs. 20%, P < .001). Subsequent survival at 90 and 365 days and treatment response were similar in both groups. Patients with PDH were more often hospitalized (95.7% vs. 60%, P = .006); however, once admitted, there were no differences in hospital length of stay or intensive care unit admission rate. The challenges of diagnosing histoplasmosis based on clinical presentation alone highlight the need for heightened awareness of these entities especially given the recent reports on expanded endemicity and delays in diagnosis.

Histoplasmosis is the most common endemic mycosis in North America. This article summarizes the clinical features, risk factors, and outcomes in patients who developed disseminated disease compared to more localized forms of histoplasmosis.

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

BACKGROUND: Since 2020 the World Health Organization (WHO) recommends Histoplasma antigen detection for the diagnosis of disseminated histoplasmosis (DH) in people living with HIV (PLHIV). OBJECTIVE: 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'. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Role of recombinant Histoplasma capsulatum 100-kilodalton antigen in the diagnosis of histoplasmosis among HIV/AIDS patients: Antigenuria and antibodies detection.

BACKGROUND: Diagnosing progressive disseminated histoplasmosis (PDH) is still challenging in many countries where this disease is highly endemic. Definitive diagnosis is established by culture and/or by cytology/histopathology but both procedures have limited sensitivity and cultures are time-consuming. Antibodies detection by immunodiffusion has a low sensitivity in immunocompromised individuals. Commercially available antigen detection assays have high sensitivity in PDH cases; however, they are expensive and only performed in few laboratories. AIMS: To describe the potential use of a novel ELISA for antibodies testing and a dot blot assay for antigen testing for diagnosing PDH using the recombinant 100 kDa protein of Histoplasma capsulatum (Hcp100) and their polyclonal antibodies as novel reagents, respectively. METHODS: Serum and urine samples from a cohort of patients with HIV/AIDS and proven PDH were studied for the detection of anti-Hcp100 antibodies by ELISA and Hcp100 antigen by dot blot, respectively. Sensitivity, specificity and cross-reactions with other diseases were estimated for each assay and compared with those obtained using histoplasmin (HMN) as a reagent for antibodies detection by ELISA and immunodiffusion, and using a commercial antigenuria test. RESULTS: Antibodies detection by the Hcp100 ELISA demonstrated 78.6% sensitivity and 88.4% specificity, versus 85.7% sensitivity and 81.0% specificity for the HMN ELISA and 26.1% sensitivity and 100% specificity for the immunodiffusion assay. Antigen detection by the Hcp100 dot blot demonstrated 89.3% sensitivity and 97.0% specificity versus 82.1% sensitivity and 90.9% specificity for the commercial test. CONCLUSION: The immunoassays described herein based on Hcp100 would be a valuable screening tool for diagnosing PDH.

Comparison of Blood (1->3)-ß-d-Glucan Levels in AIDS-Related Pneumocystis jirovecii Pneumonia and AIDS-Related Progressive Disseminated Histoplasmosis.

In this retrospective study, (1->3)-ß-d-glucan (B-glucan) was an unreliable marker for AIDS-related Pneumocystis jirovecii pneumonia (PCP) because a high percentage of participants with progressive disseminated histoplasmosis and respiratory symptoms had a positive B-glucan result. Where histoplasmosis is common, attributing B-glucan positivity to PCP without further testing risks misdiagnosis.

Review of diagnostic methods and results for HIV-associated disseminated histoplasmosis: Pathologists are not sufficiently involved.

OBJECTIVES: Disseminated histoplasmosis is a major killer of HIV-infected persons in Latin America. Antigen detection, fungal culture and Polymerase Chain Reaction are often not available, but cytology and histology are present in most hospitals and may offer a diagnostic alternative. In this study, we review 34 years of clinical experience to describe the roles of cytology and histology in diagnosing disseminated histoplasmosis. METHODS: Retrospective multicentric study of 349 patients between 1 January 1981 and 1 October 2014 with confirmed disseminated histoplasmosis. RESULTS: Around 32/214 (14.9%) of samples were screened using cytopathology, as were 10/101 (9.9%) bronchoalveolar lavage samples and 5/61 (8.2%) of spinal fluid samples. The samples most commonly sent to pathology were liver biopsies, lower digestive tract and lymphnode biopsies; the greatest proportion of positive results were found in lower digestive tract (43/59 (72.9%) positives), lymph node (39/63 (66.1%)), and liver (38/75 (50.7%)) samples. Overall, 97.2% of bone marrow and 97% of bronchoalveolar lavage samples were directly examined by a mycologist. Positive direct examination was independently associated with death (aHR = 1.5 (95%CI = 1-2.2)). CONCLUSIONS: Opportunities for a rapid diagnosis were regularly missed, notably for bone marrow samples, which could have been examined using staining methods complementary to those of the mycologist.

Intractable hypercalcemia in a patient with multiple myeloma: An infectious etiology.

Hypercalcemia is a common laboratory finding in patients with malignancy, as well as with granulomatous disease. We report the case of a 75-year-old man with multiple myeloma (MM) who presented with generalized weakness, fever, and intractable hypercalcemia. The hypercalcemia proved difficult to treat despite well-controlled MM, as well as adequate use of bisphosphonates and calcitonin. Biopsy of sub-centimeter mesenteric adenopathy was significant for Histoplasma capsulatum and negative for malignancy, suggesting disseminated gastrointestinal histoplasmosis as the sole etiology for uncontrolled hypercalcemia. He was successfully treated with voriconazole. Disseminated histoplasmosis can be fatal if left untreated and warrants vigilance of non-malignant etiologies of hypercalcemia. While hypercalcemia is a common clinical manifestation of MM, our patient is an exemplar of maintaining a broader differential diagnosis in immunocompromised hosts.

Cytomegalovirus and disseminated histoplasmosis-related hemophagocytic lymphohistiocytosis syndrome in an HIV-patient late presenter with IRIS: a case report.

BACKGROUND: Hemophagocytic lymphohistiocytosis syndrome (HLS) is an immune-mediated life-threatening disease considered as a medical emergency, with a potentially fatal multisystem inflammatory outcome. We present a patient that developed HLS and was able to be diagnosed efficiently with the help of an academic research institute of immunology. CASE PRESENTATION: A 21 years old male Mexican with human immunodeficiency virus (HIV), late presenter; who developed cytomegalovirus (CMV) infection and a disseminated histoplasmosis-related HLS, as part of an immune reconstitution inflammatory syndrome (IRIS). The patient required a long course of corticotherapy, intravenous immunoglobulin and massive transfusions (more than 10 units in 24 h, and a total of 83 units), besides amphotericin-B and ganciclovir treatment. An academic research institute of immunology aided in the accurate diagnosis of HLS with the implementation of tests not available within the hospital, thus improving the care provided to the patient. The patient recovered, was discharged, and continue to improve. CONCLUSION: The objective of this report is to highlight the importance of having multidisciplinary support, including basic medical sciences groups providing specific tests that are sometimes very difficult to get, which provides a benefit to patients in the well-aimed diagnosis as part of applied translational medicine.

Disseminated histoplasmosis in an immunocompetent individual diagnosed with gastrointestinal endoscopy: a case report.

BACKGROUND: Histoplasmosis is one of the invasive fungal infections and presents with symptoms mainly in the lungs. Disseminated histoplasmosis (DH) is rare and its lesions in the gastrointestinal tract are even uncommon. The concomitant involvement of the upper and lower gastrointestinal tract has never been described in the immunocompetent individuals. CASE PRESENTATION: A 44-year-old immunocompetent Chinese man presented with fever, hepatosplenomegaly, fungal esophagitis and protuberant lesions with central depression and erosion along the mucous membrane of the colon. The patient was diagnosed as disseminated histoplasmosis by gastrointestinal endoscopy. CONCLUSIONS: Histoplasmosis should be taken caution in patients with fever and hepatosplenomegaly. Actions should be taken to avoid its disseminated infection associated high mortality.

Disseminated histoplasmosis and AIDS: a prospective and multicentre study to evaluate the performance of different diagnostic tests.

The burden of histoplasmosis has been poorly documented in most of the endemic areas for the disease, including Brazil. Also, modern non-culture-based diagnostic tests are often non-available in these regions. This was a prospective cohort study in HIV-infected patients with suspected disseminated disease evaluated with different diagnostic tests. Patients were enrolled in three referral medical centres in Porto Alegre, Brazil. Among 78 evaluated patients, disseminated histoplasmosis was confirmed in eight individuals (10.3%) by the means of classical (culture/histopathology) tests. Antigen detection in the urine was found to be more sensitive: IMMY® ALPHA ELISA detected 13 positive cases (16.7%) and the in-house ELISA test developed by the Centers for Disease Prevention and Control (CDC) detected 14 (17.9%). IMMY® and CDC tests provided concordant results in 96.2% of cases. This is the first study to compare the performance of the in-house CDC ELISA test with the IMMY® commercial test for the diagnosis of histoplasmosis, and a high degree of concordance was observed. The study revealed that H. capsulatum is an important agent of disseminated disease in AIDS patients in Brazil, reinforcing the importance of making available modern diagnostic tests as well as safer antifungal agents for the treatment of histoplasmosis.

Reconstitution Inflammatory Syndrome Like Reactive Hemophagocytic Syndrome Associated with Disseminated Histoplasmosis in a HIV Patient.

We describe an unusual clinical association of disseminated histoplasmosis with reactive hemophagocytic syndrome. We report the case of a new HIV-positive patient with reconstitution inflammatory syndrome like reactive hemophagocytic syndrome associated with disseminated histoplasmosis. We describe the clinical case, the procedures performed, the treatment provided and the patient's evolution. A figure of liver biopsy Grocott's silver methenamine stain that shows lots of uniform ovoid yeasts in portal spaces' macrophages that supports the diagnosis of disseminated histoplasmosis in our case.

An Unusual Presentation of Disseminated Histoplasmosis: Case Report and Review of Pediatric Immunocompetent Patients from India.

Histoplasmosis is a progressive disease caused by dimorphic intracellular fungi and can prove fatal. Usually, it is present in immunocompromised individuals and immunocompetent individuals in the endemic zones. We report an unusual presentation of progressive disseminated histoplasmosis. The patient in the present case report was immunocompetent child and had fever, bone pains, gradual weight loss, lymphadenopathy and hepatosplenomegaly. Disseminated histoplasmosis (DH) was diagnosed on microscopic examination and fungal culture of bone marrow, blood, skin biopsy and lymph node aspirate. The patient died on seventh day of amphotericin B. In the absence of predisposing factors and classical clinical presentation of febrile neutropenia, lung, adrenal and oropharyngeal lesions, the disease posed a diagnostic challenge. Progressive disseminated histoplasmosis in children can be fatal despite timely diagnosis and therapy. In India, disseminated histoplasmosis is seen in immunocompetent hosts. All the pediatrics immunocompetent cases from India are also reviewed.

Cutaneous histoplasmosis in renal transplant recipients.

Cutaneous histoplasmosis is a rare entity, although it can be seen in a substantial portion of renal transplant recipients with disseminated disease. The prognosis of disseminated disease is worse than isolated cutaneous involvement, and significant delays in diagnosis are reported. We reviewed reports of cutaneous histoplasmosis with and without dissemination in the setting of renal transplantation to examine incidence, timing of diagnosis, clinical features, and prognosis. Remarkable morphologic variability and the non-specific appearance of skin findings suggest that tissue culture is required for definitive diagnosis. Cutaneous lesions represent an easily accessible source for early diagnosis.

Disseminated histoplasmosis in allogeneic bone marrow transplant: a diagnosis not to be missed.

Immunosuppressed patients are at highest risk for disseminated histoplasmosis, but only a few cases have been reported in hematopoietic stem cell transplant recipients. We report a case of disseminated histoplasmosis in an allogeneic bone marrow transplant recipient residing in a non-endemic area. Diagnosis was first suspected based on a peripheral blood smear.

Disseminated histoplasmosis in HIV-infected patients: determinants of relapse and mortality in a north-eastern area of Brazil.

Many relapses and deaths resulting from disseminated histoplasmosis (DH) in acquired immunodeficiency syndrome (AIDS) patients have been observed in an endemic area in north-eastern Brazil. The objective of this study was to evaluate the risk factors associated with the clinical outcomes of DH/AIDS coinfection in patients from the state of Ceará, Brazil. A retrospective cohort of AIDS patients, after their hospital discharge due to first DH episode in the period 2002-2008, was followed until December 31, 2010, to investigate the factors associated with relapse and mortality. A total of 145 patients were evaluated in the study. Thirty patients (23.3%) relapsed and the overall mortality was 30.2%. The following variables were significantly (P < 0.05) associated with relapse and overall mortality (univariate analysis): non-adherence to highly active antiretroviral therapy (HAART), irregular use of an antifungal, non-recovery of the CD4+ count and having AIDS before DH; histoplasmosis relapse was also significantly associated with mortality. In the multivariate analysis, non-adherence to HAART was the independent risk factor that was associated with both relapse (Adj OR = 6.28) and overall mortality (Adj OR = 8.03); efavirenz usage was discovered to be significant only for the overall mortality rate (Adj OR = 4.50). Adherence to HAART was the most important variable that influenced the outcomes in this specific population.

Haemophagocytic lymphohistiocytosis secondary to disseminated histoplasmosis in an immunocompetent patient.

Haemophagocytic lymphohistiocytosis secondary to Histoplasma infection is rare and almost always occurs in immunocompromised hosts. We report a 32-year-old immunocompetent man presenting with a nonspecific febrile illness found to have disseminated histoplasmosis and associated haemophagocytic lymphohistiocytosis. The diagnosis was confirmed on histopathological examination and PCR of liver and bone marrow biopsies. He was successfully treated with steroids, intravenous immunoglobulin and itraconazole.

Disseminated Histoplasmosis Diagnosed in an Immunocompetent Patient from a Non-Endemic Area: Neglected or Emerging Disease?

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.

Gastrointestinal histoplasmosis with small intestinal perforation: 20-year experience.

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.