Histoplasmosis In AIDS Patients Research Articles

Evaluation of Nephrotoxicity of Liposomal Amphotericin in Three Administration Regimens for the Treatment of Disseminated Histoplas-mosis in AIDS Patients

Evaluation of Nephrotoxicity of Liposomal Amphotericin in Three Administration Regimens for the Treatment of Disseminated Histoplas-mosis in AIDS Patients

Progressive disseminated histoplasmosis in HIV-positive patients.

Histoplasmosis is the most common endemic mycosis among people living with advanced HIV infection. Describe general aspects and challenges of this disease and its association with HIV. Review of literature. Articles found using different combinations of terms including "disseminated histoplasmosis" and AIDS/HIV or immunosuppression in PubMed, Scopus, WHO Global health library, and Scielo database. We look for information on epidemiology, pathogenesis, diagnosis, and treatment of histoplasmosis in AIDS patients. Histoplasmosis is caused by Histoplasma capsulatum, a dimorphic fungus encountered throughout the world, mainly in soil enriched with bat and bird excreta. Progressive disseminated histoplasmosis is the main presentation of this mycosis in people living with advanced HIV and is fatal if left untreated. Symptoms include a systemic disease characterized by fever, weight loss, night sweats, skin manifestations, hepatomegaly, splenomegaly, and septic shock. Diagnostic tests include culture, visualization of H. capsulatum by direct and histopathological examination, serology, antigen, molecular, and skin testing. Patients with disseminated disease require aggressive and prolonged treatment to eradicate the pathogen and include amphotericin B and itraconazole. In many low income countries of endemic regions, histoplasmosis in HIV-positive patients is often undiagnosed or misdiagnosed as another opportunistic infection, due to the similarity in clinical manifestations and to the paucity of better diagnostic tests. Histoplasmosis remains a neglected disease. Few studies about the disease and expensive treatments make it difficult to reduce the morbidity and mortality of this condition. Public health services and physicians must be aware of histoplasmosis' burden among the HIV-positive population.

Current burden of serious fungal infections in Republic of Congo.

The Republic of Congo (RoC) is characterised by a high prevalence of tuberculosis and HIV/AIDS, which largely drive the epidemiology of serious fungal infections. We aimed to estimate the current burden of serious fungal infections in RoC. Using local, regional or global data and estimates of population and at-risk population groups, deterministic modelling was employed to estimate national incidence or prevalence of the most serious fungal infections. Our study revealed that about 5.4% of the Congolese population (283450) suffer from serious fungal infections yearly. The incidence of cryptococcal meningitis, Pneumocystis jirovecii pneumonia and disseminated histoplasmosis in AIDS patients was estimated at 560, 830 and 120 cases per year. Oral and oesophageal candidiasis collectively affects 12320 HIV-infected patients. Chronic pulmonary aspergillosis, 67% post-tuberculosis, probably has a prevalence of 3420. Fungal asthma (allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitisation) probably has a prevalence of 3640 and 4800, although some overlap due to disease definition is likely. The estimated prevalence of recurrent vulvovaginal candidiasis and tinea capitis is 85440 and 178400 respectively. Mostly related to agricultural activity, fungal keratitis affects an estimated 700 Congolese yearly. These data underline the urgent need for an intensified awareness towards Congolese physicians to fungal infections and for increased efforts to improve diagnosis and management of fungal infections in the RoC.

Accuracy of Buffy Coat in the Diagnosis of Disseminated Histoplasmosis in AIDS-Patients in an Endemic Area of Brazil.

The buffy coat is obtained routinely for disseminated histoplamosis (DH) diagnosis in Ceará, Brazil. The aim of this study is to describe the accuracy of staining smears for Histoplasma in the buffy coat of AIDS-patients with DH. From 2012–2013, all results of stained buffy coat smears and culture for fungi performed at São José Hospital were recorded. In total, 489 buffy coats of 361 patients were studied; 19/361 (5.3%; 95%CI = 2.9–7.6%) had positive direct examination stained smears for Histoplasma and 61/361 (16.9%; 95%CI = 13.0–20.8%) had growth in culture. For those with positive Histoplasma cultures, the CD4 count was significantly lower (139.3 vs. 191.7cells/µL; p = 0.014) than others, and death was 18%. The sensitivity and specificity of stained smears was 25.9% and 100%, respectively. A second test, performed up to 36 days from the first one, increased the sensitivity of stained smears to 32.2%. Stained smears of buffy coat have low accuracy; nonetheless, they are easy to perform and can give a quick diagnosis in low-resource endemic areas. Despite the decrease in mortality, it is not yet to the low levels observed in areas that have better and more efficient methods.

Predictive factors for disseminated histoplasmosis in AIDS patients with fever admitted to a reference hospital in Brazil.

In many settings, the lack of sensitive biomarkers of disseminated histoplasmosis (DH) leads to a clinical reliance on older diagnostic methods and delayed treatment initiation. The early recognition of DH is critical for survival, especially in patients with human immunodeficiency virus (HIV). This study aimed to identify clinical and laboratory findings associated with the definitive diagnosis of DH in low-income HIV patients in endemic areas. Febrile AIDS patients with suspected DH who were admitted to a reference hospital in northeastern Brazil from January 2006 to January 2007 were evaluated for clinical and laboratory findings associated with DH diagnosis. One hundred seventeen patients with fever were included, and 48 (41%) cases of DH were determined by Histoplasma capsulatum identification. A higher fever (≥38.5ºC), maculopapular/papular rash, splenomegaly, hepatomegaly, wheezing, hemoglobin ≤9.5g/dL, platelets ≤80,000/µL, CD4 count ≤75/µL, aspartate aminotransferase (AST) level ≥2.5 times the upper limit of normal (ULN), lactate dehydrogenase (LDH) ≥5times the ULN; and international normalized ratio (INR) >2 times the ULN were significantly associated with DH. A multivariable analysis identified hepatomegaly [adjusted (a) prevalence ratio (PR)= 1.96; 95% confidence interval (CI): 1.21-3.16), CD4 count ≤75/µL (aPR = 2.02; 95% CI: 1.06-3.83), LDH ≥5 times the ULN (aPR = 2.23; 95% CI: 1.44-3.48), and maculopapular/papular rash (aPR = 1.70; 95% CI: 1.02-2.83) were independent risk factors for DH. These easily assessed parameters can facilitate clinical decision-making for febrile AIDS patients with suspected DH in low socioeconomic and Histoplasma-endemic regions.

Central Nervous System Histoplasmosis in Acquired Immunodeficiency Syndrome

BackgroundInvolvement of the central nervous system (CNS) by Histoplasma capsulatum in AIDS is uncommon and not easily recognized. Materials and MethodsCNS histoplasmosis cases from our institution were identified by a retrospective chart review from 2004-2014. A thorough literature search was performed for additional cases and their characteristics were compared. Clinical findings, treatment and outcomes are discussed. ResultsA total of 5 cases from our institution were identified. They had a clinical presentation that included classic signs of meningitis, often with evidence of disseminated involvement, and was typically severe with important neurological impairment. These cases were treated with antifungal agents, including a lipid amphotericin B formulation and azole drugs, but eventually 3 experienced nonresolution of their disease likely because of lack of adherence to therapy and died from their infection. The clinical presentation, treatment and outcome of these cases did not significantly differ from cases found in the review of the literature. ConclusionsClinicians practicing in endemic areas should be aware of this rare but serious form of histoplasmosis. The recognition of 5 cases of CNS histoplasmosis in AIDS patients from a single institution suggests that histoplasmosis should be included in the differential diagnosis of the CNS complications of AIDS.

Burden of serious fungal infections in Trinidad and Tobago.

The information on the prevalence of fungal infections in the Caribbean region including Trinidad and Tobago (population 1,339,000 million) is scanty. Tinea capitis is common in children, being predominant in those of African descent, with no definitive estimate. Asthma is also common affecting 77,000-139,000 adults with an estimated 1927-3491 affected by allergic bronchopulmonary aspergillosis (ABPA) and 2544-4608 with severe asthma and fungal sensitisation (SAFS). An estimated 23,763 women have ≥4 attacks of vaginal candidiasis annually. Among the estimated 14,000 HIV-infected patients, 750 cases of oesophageal candidiasis, 400 cases of Pneumocystis pneumonia (PCP) and 50 cases of cryptococcal meningitis are anticipated. Histoplasma capsulatum is endemic in the islands with a 49% skin positivity rate in those <60 years old. Three cases of cutaneous histoplasmosis in AIDS patients have been reported. Three cases of pulmonary histoplasmosis were reported among German biologists following exposure to bats in a cave in Trinidad. Using a low mean international incidence figure for candidaemia of 5/100,000, 67 cases of candidaemia are estimated. The burden of fungal infections in Trinidad and Tobago is considerable and requires appropriate diagnostic and clinical expertise.

A complementary tool for management of disseminated Histoplasma capsulatum var. capsulatum infections in AIDS patients

In South America, disseminated histoplasmosis due to Histoplasma capsulatum var. capsulatum (H. capsulatum), is a severe and frequent opportunistic infection in AIDS patients. In areas outside the USA where specific-Histoplasma antigen detection is not available, the diagnosis is difficult. With the galactomannan antigen (GM) detection, a test commonly used for invasive aspergillosis diagnosis, there is a cross-reactivity with H. capsulatum that can be helpful for the diagnosis of histoplasmosis. The aim of this study was to evaluate the GM detection for the diagnosis of disseminated histoplasmosis in AIDS patients. The performance of the GM detection was evaluated with serum collected in French Guiana where H. capsulatum is highly endemic. Sera from AIDS patients with disseminated histoplasmosis occurring from 2002 to 2009 and from control HIV-positive patients without histoplasmosis were tested with the GM detection and Histoplasma-specific antibody detection (IEP). In 39 AIDS patients with proven disseminated histoplasmosis, the sensitivity of the Histoplasma IEP was only 35.9% and was linked to the TCD4+ lymphocyte level. For the GM detection, the sensitivity (Se) was 76.9% and specificity (Sp) was 100% with the recommended threshold for aspergillosis diagnosis (0.5). The test was more efficient with a threshold of 0.4 (Se: 0.82 [95% CI: 0.66–0.92], Sp: 1.00 [95% CI: 0.86–1.00], LR+: >10, LR−: 0.18). This study confirms that the GM detection can be a surrogate marker for the diagnosis of disseminated histoplasmosis in AIDS patients in endemic areas where Histoplasma EIA is not available.

Antigen negative gastrointestinal histoplasmosis in an AIDS patient

Patient: Female, 51Final Diagnosis: Gastrointestinal histoplasmosisSymptoms: Abdominal pain • nausea • vomitingMedication: —Clinical Procedure: —Specialty: Gastroenterology and HepatologyObjective:Adverse events of drug therapyBackground:Gastrointestinal involvement in patients with disseminated histoplasmosis is considered common since the organism is identified in the GI tract of approximately 70–90% of autopsy cases. This infection is rarely recognized by clinicians due to its non-specific symptoms. Lesions may occur anywhere in the GI tract but most commonly affects the terminal ileum. Patients present with GI bleeding, intestinal obstruction, ulcerations, masses, and peritonitis. Serum and urine serological antigens are useful for diagnosis because they are positive in over 90% of patients with disseminated disease but may be falsely negative in patients with localized GI involvement. Although histopathology and tissue cultures are specific, limitations include insensitivity and need for invasive procedures. Antifungal agents include intravenous amphotericin B for severe or unstable disease and oral itraconazole for stable disease.Case Report:A 51-year-old HIV positive female presented with abdominal pain, nausea and vomiting. A CT scan of the abdomen revealed circumferential narrowing around a segment of the sigmoid colon with the cecum demonstrating irregular thickened walls. A biopsy of an obstructing duodenal mass found on endoscopy revealed granulomatous inflammation and budding yeasts consistent with Histoplasma spp. She was started on intravenous liposomal amphotericin B and after 2 weeks switched to itraconazole oral solution. Urine and serum histoplasma antigens sent out 2 weeks after antifungal treatment were negative.Conclusions:This case report illustrates the importance of recognizing gastrointestinal histoplasmosis in AIDS patients presenting with non-specific GI symptoms.

Histoplasmosis in HIV-positive patients in Ceará, Brazil: clinical-laboratory aspects and in vitro antifungal susceptibility of Histoplasma capsulatum isolates

This study contains a descriptive analysis of histoplasmosis in AIDS patients between 2006 and 2010 in the state of Ceará, Brazil. Additionally, the in vitro susceptibility of Histoplasma capsulatum isolates obtained during this period was assessed. We report 208 cases of patients with histoplasmosis and AIDS, describing the epidemiological, clinical, laboratory and therapeutic aspects. The in vitro antifungal susceptibility test was carried out by the microdilution method, according to Clinical and Laboratory Standards Institute, with H. capsulatum in the filamentous and yeast phases, against the antifungals amphotericin B, fluconazole, itraconazole, voriconazole and caspofungin. In 38.9% of the cases, histoplasmosis was the first indicator of AIDS and in 85.8% of the patients the CD4 cell count was lower than 100 cells/mm(3). The lactate dehydrogenase levels were high in all the patients evaluated, with impairment of hepatic and renal function and evolution to death in 42.3% of the cases. The in vitro susceptibility profile demonstrated there was no antifungal resistance among the isolates evaluated. There was a significant increase in the number of histoplasmosis cases in HIV-positive patients during the period surveyed in the state of Ceará, northeastern Brazil, but no antifungal resistance among the recovered isolates of H. capsulatum.

Production and Evaluation of Reagents for Detection of Histoplasma capsulatum Antigenuria by Enzyme Immunoassay

The detection of urinary Histoplasma capsulatum polysaccharide antigen (HPA) by enzyme immunoassay (EIA) has proven useful for the presumptive diagnosis of histoplasmosis in AIDS patients. Assay limitations include (i) detection of a largely uncharacterized antigen and (ii) difficulty in reproducibly generating antibodies for use in the EIA. To improve antibody production for use in this test and to better understand the antigen being detected, we compared rabbit antibodies elicited using various immunization schedules, routes, and H. capsulatum-derived antigens. Antibodies were evaluated by EIA for their ability to detect purified H. capsulatum C antigen (C-Ag) and antigenuria. Reported as enzyme immunoassay (EI) units (the A(450) with antigen divided by the A(450) without antigen), results demonstrated that intravenous immunization of rabbits with whole, killed yeast-phase cells (yeast-i.v. regimen) produced antibodies giving the highest EI values in the C-Ag EIA (mean EI units +/- standard deviation, 14.9 +/- 0.6 versus 6.4 +/- 0.4 for rabbits immunized with C-Ag versus 2.4 +/- 0.3 for all other regimens combined). Yeast-i.v. antibodies were highly sensitive for the detection of antigenuria in patients with histoplasmosis, as shown by the following results: 12/12 patients compared to 10/12, 6/12, 3/12, and 3/12, respectively, for antibodies from rabbits immunized with (i) C-Ag; (ii) whole, killed yeast-phase cells administered subcutaneously and intramuscularly; (iii) yeast-phase culture filtrates; and (iv) HPA-positive urine. Rabbits immunized using the yeast-i.v. regimen also gave higher peak antibody titers than rabbits immunized by any other regimen (P < 0.03), and their antibodies were most comparable in reactivity to antibodies produced for use in the standard HPA-EIA test (P < 0.001). Therefore, rabbits immunized using the yeast-i.v. regimen produced the most sensitive antibodies with the highest titers for detection of C-Ag and antigenuria in histoplasmosis patients.

P969 Mucocutaneous manifestations of disseminated histoplasmosis in AIDS patients: special aspects in a Latin American population

P969 Mucocutaneous manifestations of disseminated histoplasmosis in AIDS patients: special aspects in a Latin American population

Colonic Histoplasmosis Presenting as Colon Cancer in the Nonimmunocotnpromised Patient: Report of a Case and Review of the Literature

Histoplasma capsulatum is an important pathogen that is the most commonly diagnosed endemic mycosis in the gastrointestinal tract of immunocompromised hosts. Failure to recognize and treat disseminated histoplasmosis in AIDS patients invariably leads to death. Gastrointestinal manifestations frequently involve the terminal ileum and cecum, and depending on the layer of bowel wall involved present as bleeding, obstruction, perforation, or peritonitis. Because they can be variable in appearance, they may be mistaken for Crohn's disease or malignant tumors. Four distinct pathologic patterns of GI histoplasmosis have been described that all have differing clinical presentations. We report a case of a non-AIDS patient who presented with a near-obstructing colonic mass suspicious for advanced malignancy but was found to have histoplasmosis on final pathology. The patient underwent successful operative resection, systemic antifungal therapy, and extensive workup for immunosuppressive disorders, which were negative. The patient was from an area in Mexico known to be endemic for histoplasmosis. This is the first report of a colonic mass lesion occurring in a non-AIDS patient, and review of the worldwide literature regarding GI histoplasmosis reveals excellent long-term survival with aggressive therapy. We discuss the surgical and medical management of colonic histoplasmosis in this report.

Treatment of Disseminated Histoplasmosis in AIDS Patients

Disseminated histoplasmosis is a rare, severe, and life-threatening infection in HIV-positive patients with low CD4-cell counts. These authors compared results of 2 therapeutic studies: 1 using itraconazole during 1991 and 1992, the other using liposomal ampothericin B from 1995 to 1999. In the first study, 59 HIV-positive patients with disseminated histoplasmosis were treated with 300 mg …

Disseminated histoplasmosis and AIDS: clinical aspects and diagnostic methods for early detection.

Disseminated histoplasmosis in AIDS patients is the focus of this paper. Cutaneous lesions are reported as a frequent clinical sign. Bone marrow aspiration and biopsy, blood cultures (lysis-centrifugation technique), bronchoalveolar lavage, and skin lesion scrapings are the most effective diagnostic methods. The identification of a specific antigen in blood and urine may be a rapid means of evaluation and follow-up of patients with this disease.

Endemic mycoses: a treatment update.

Endemic mycoses remain a major public health problem in several countries and they are becoming increasingly frequent with the spread of HIV infection. Amphotericin B remains the drug of choice during the acute stage of life-threatening endemic mycoses occurring in both immunocompetent and immunocompromised hosts. Ketoconazole is effective in non-AIDS patients with non-life-threatening histoplasmosis, blastomycosis, or paracoccidioidomycosis. Itraconazole is the treatment of choice for non-life-threatening Histoplasma capsulatum or Blastomyces dermatitidis infections occurring in immunocompetent individuals and is the most efficient secondary prophylaxis of histoplasmosis in AIDS patients. Itraconazole is also effective in lymphocutaneous and visceral sporotrichosis, in paracoccidioidomycosis, for Penicillum marneffei infection, and is an alternative to amphotericin B for Histoplasma duboisii infection. Coccidioidomycosis may be effectively treated with prolonged and sometimes life-long itraconazole or fluconazole therapy. Fluconazole has relatively poor efficacy against histoplasmosis, blastomycosis and sporotrichosis. New antifungal agents have been tested in vitro or in animal models and may soon be evaluated in clinical trials.

Serodiagnosis of histoplasmosis, paracoccidioidomycosis and penicilliosis marneffei; current status and future trends

Effective serodiagnosis of systemic fungal infections is of increasing importance, particularly with regard to the identification of infection with Histoplasma capsulatum, Paracoccidioides brasiliensis and Penicillium marneffei. Methodology has been based either around antibody or antigen detection, although there is clear overlap between the two. Antibody-based detection systems for the diagnosis of histoplasmosis, paracoccidioidomycosis and penicilliosis marneffei have now begun to incorporate a range of highly purified and well-characterized antigens, in contrast to the situation of a few years ago when relatively crude preparations derived from either whole cells or culture filtrate were used. The application of such antigens offers improvements in reproducibility and specificity, although the detection of meaningful antibody responses in immunosuppressed individuals remains a problem. Partly as a consequence of this a great deal of attention has focused on the development of antigen detection assays, and such methods have proved particularly successful, as for instance in the serodiagnosis of histoplasmosis in AIDS patients. The recent utilization of monoclonal antibodies in the development of antigen detection methods for the diagnosis of histoplasmosis and paracoccidioidomycosis offers further scope for improvement in this area.

Diagnosis of Systemic Histoplasmosis in AIDS Patients Reply

Diagnosis of Systemic Histoplasmosis in AIDS Patients Reply

Disseminated histoplasmosis in AIDS: findings on chest radiographs.

Our objective was to determine the findings of disseminated histoplasmosis on chest radiographs of patients with AIDS. Chest radiographs of 50 AIDS patients with documented extrapulmonary histoplasmosis were analyzed retrospectively. The radiographs were evaluated for the presence of parenchymal opacities, pleural effusions, adenopathy, cavitation, and calcified granulomas and lymph nodes. A modification of the International Labour Office scheme was used to classify parenchymal abnormalities as nodular, linear or irregular, reticulonodular, or air-space opacities. Abnormalities were present on radiographs in 23 patients. Nodular opacities were present in 10 patients and were diffusely distributed in nine patients. Linear or irregular opacities were present in seven patients, with diffuse distribution in four and limited involvement in three. Air-space opacities were present in seven patients; the distribution varied from segmental to diffuse involvement of the lung. Small pleural effusions were present in five patients. Adenopathy and Kerley's B lines were each present in three patients. In 27 patients, the chest radiographs were normal. Four of these patients had clinical or microbiological evidence of lung involvement. The chest radiographic findings of disseminated histoplasmosis in AIDS patients are varied and nonspecific. The presence of diffuse nodular or linear/irregular opacities in an AIDS patient, especially one who resides in or has resided in an endemic area, should suggest the possibility of disseminated histoplasmosis. Normal findings on chest radiographs do not exclude disseminated infection or lung involvement.