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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.
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Anfotericina B , Antifúngicos , Histoplasmose , Itraconazol , Humanos , Histoplasmose/tratamento farmacológico , Histoplasmose/epidemiologia , Histoplasmose/diagnóstico , Masculino , Feminino , Antifúngicos/uso terapêutico , Pessoa de Meia-Idade , Colômbia/epidemiologia , Adulto , Anfotericina B/uso terapêutico , Itraconazol/uso terapêutico , Triazóis/uso terapêutico , Resultado do Tratamento , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Idoso , Histoplasma/isolamento & purificação , Histoplasma/efeitos dos fármacosRESUMO
Among people living with HIV (PLHIV), progressive disseminated histoplasmosis (PDH) represents an important cause of mortality. Since antigen detection allows a rapid diagnosis and the instauration of a specific treatment this study aimed to evaluate the analytical performance of the Hcp100 dot blot, an in-house assay that detects the Histoplasma capsulatum 100-kilodalton antigen in urine and compare it with 2 commercially available assays the Histoplasma Urine Antigen Lateral Flow Assay (MVD-LFA) (MiraVista® Diagnostics) and the Clarus Histoplasma Galactomannan EIA (Clarus HGM) (IMMY). Urine specimens from 23 PLHIV with PDH, 13 patients with other infectious diseases, and 20 healthy individuals were tested. The Hcp100 dot blot showed higher sensitivity (87.0%), specificity (97.0%) and accuracy (92.9%) than the MVD-LFA (73.9%, 78.8%, and 76.8%, respectively) and the Clarus HGM (78.3%, 90.9%, and 85.7%, respectively). The Hcp100 dot blot had high analytical performance and would be a valuable screening tool for diagnosing PDH among PLHIV.
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Síndrome da Imunodeficiência Adquirida , Histoplasmose , Humanos , Histoplasmose/diagnóstico , Histoplasmose/urina , Histoplasma , Sensibilidade e Especificidade , Antígenos de FungosRESUMO
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.
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Síndrome da Imunodeficiência Adquirida , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Histoplasmose , Humanos , Histoplasmose/tratamento farmacológico , Antifúngicos/efeitos adversos , HIV , Estudos Prospectivos , Síndrome da Imunodeficiência Adquirida/tratamento farmacológicoRESUMO
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.
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Síndrome da Imunodeficiência Adquirida , Histoplasmose , Humanos , Histoplasmose/diagnóstico , Histoplasma , Antígenos de Fungos/análise , Ensaio de Imunoadsorção EnzimáticaRESUMO
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.
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Histoplasmose , Humanos , Histoplasmose/diagnóstico , Histoplasmose/epidemiologia , Histoplasma , Estudos Retrospectivos , Brasil/epidemiologia , Antígenos de Fungos , Técnicas Imunoenzimáticas , Sensibilidade e EspecificidadeRESUMO
A 54 year-old man with lymphopenia secondary to lymphatic filariasis was admitted with dry cough, fever and wasting syndrome. He was diagnosed with sarcoidosis and therapy with corticosteroid was initiated. The patient evolved with worsening of the symptoms. Histoplasma species was recovered in lung biopsy tissue, lung tissue culture, and bone marrow aspirate. The authors describe the first case of disseminated histoplasmosis secondary to lymphatic filariasis, followed by a literature review. 2012 Elsevier Ltd. All rights reserved.
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A 66-year-old man presented with asymptomatic right testicular swelling. He was known to be infected with HIV and was non-adherent to treatment. He was recently treated for nasal leishmaniasis. Surgical drainage was performed and eventually, an orchiectomy was required. A post-mortem diagnosis was made of disseminated histoplasmosis. Testicular infection due to H. capsulatum is rare, with only a few cases being reported. Here we present a case of testicular histoplasmosis, followed by a literature review.
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Resumen Introducción: La histoplasmosis es una micosis sistémica en pacientes inmunodeprimidos y su epidemiología es desconocida en el país. Objetivo: Describir los datos demográficos y clínicos de pacientes con infección por VIH (IpVIH) e histoplasmosis diagnosticadas en el Laboratorio Central de Salud Pública, Asunción-Paraguay. Pacientes yMétodos: Estudio retrospectivo y transversal de pacientes con muestras positivas a Histoplasma capsulatum diagnosticados en el período 1993-2017. Resultados: Fueron diagnosticados 162 pacientes con IpVIH e histoplasmosis. El origen de los pacientes en orden de prevalencia fue: la capital Asunción, Central, Cordillera y San Pedro. La relación hombre/mujer fue 4:1 y la edad media 34,1 ± 7,7 años con un rango de 18 a 61 años. La fiebre, las lesiones en piel y las úlceras en mucosa fueron los síntomas y manifestaciones más frecuentes. Los métodos para diagnósticos más utilizados fueron las escarificaciones de piel, úlceras muco-cutáneas y las punciones de médula ósea. Conclusión: Por ser el primer reporte nacional de histoplasmosis en pacientes con IpVIH, consideramos este trabajo relevante para la base de otros estudios de micosis profunda.
Abstract Background: Histoplasmosis is a systemic mycosis in immunosuppressed patients and its epidemiology is unknown in the country. Aim: To describe the demographic and clinical data of patients with HIV infection and histoplasmosis diagnosed in the Central Public Health Laboratory, Asunción-Paraguay. Methods: Retrospective and cross-sectional study of patients with Histoplasma capsulatum positive samples diagnosed in the period 1993-2017. Results: 162 patients with HIV infection were diagnosed as histoplasmosis. The origin of the patients in order of prevalence were the capital Asunción, Central, Cordillera and San Pedro departments. The male/female ratio was 4: 1 and the mean age was 34.1 ± 7.7 years with a range of18 to 61 years. Fever, skin lesions and mucosal ulcers were the most frequent symptoms and manifestations. The most widely used diagnostic methods were scarification of skin, mucocutaneous ulcers and bone marrow punctures. Conclusion: As it is the first national report of histoplasmosis in patients with HIV infection, we consider this work relevant for the basis of other studies of deep mycosis.
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Histoplasma capsulatum is an environmental fungus commonly found in the Ohio and Mississippi River valleys, Central and South America, and Asia. The most affected areas in Argentina are the Paraná and de La Plata river basins. Patients with histoplasmosis can have a wide range of clinical presentations. Most of them are asymptomatic, while those with compromised cellular immunity are at increased risk for the disseminated form. We present the case of a patient undergoing treatment with methotrexate for seronegative arthritis who developed the disseminated form of the disease, and who represented a diagnostic challenge due to the difficulty in identifying the etiologic agent.
Histoplasma capsulatum es un hongo ambiental que se encuentra distribuido comúnmente en los valles de los ríos Ohio y Mississippi, América Central, Sudamérica y Asia. Las zonas más afectadas en Argentina son las cuencas de los ríos Paraná y de La Plata. Los pacientes con histoplasmosis tienen una amplia variedad de manifestaciones clínicas. La mayoría son asintomáticos, mientras que aquellos con compromiso de la inmunidad celular tienen un riesgo aumentado de padecer la forma diseminada. Presentamos el caso de una mujer adulta, en tratamiento con metotrexato por una artritis seronegativa, que desarrolló la forma diseminada de la enfermedad, y que representó un desafío diagnóstico debido a la dificultad para identificar el agente etiológico.
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Artrite , Histoplasmose , Argentina , Artrite/tratamento farmacológico , Feminino , Histoplasma , Histoplasmose/diagnóstico , Histoplasmose/tratamento farmacológico , Humanos , MetotrexatoRESUMO
Resumen Histoplasma capsulatum es un hongo ambiental que se encuentra distribuido comúnmente en los valles de los ríos Ohio y Mississippi, América Central, Sudamérica y Asia. Las zonas más afectadas en Argentina son las cuencas de los ríos Paraná y de La Plata. Los pacientes con histoplasmosis tienen una amplia variedad de manifestaciones clínicas. La mayoría son asintomáticos, mientras que aquellos con com promiso de la inmunidad celular tienen un riesgo aumentado de padecer la forma diseminada. Presentamos el caso de una mujer adulta, en tratamiento con metotrexato por una artritis seronegativa, que desarrolló la forma diseminada de la enfermedad, y que representó un desafío diagnóstico debido a la dificultad para identificar el agente etiológico.
Abstract Histoplasma capsulatum is an environmental fungus commonly found in the Ohio and Mississippi River valleys, Central and South America, and Asia. The most affected areas in Argentina are the Paraná and de La Plata river basins. Patients with histoplasmosis can have a wide range of clinical presentations. Most of them are asymptomatic, while those with compromised cellular immunity are at increased risk for the disseminated form. We present the case of a patient undergoing treatment with methotrexate for seronegative arthritis who developed the disseminated form of the disease, and who represented a diagnostic challenge due to the difficulty in identifying the etiologic agent.
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Humanos , Feminino , Artrite/tratamento farmacológico , Histoplasmose/diagnóstico , Histoplasmose/tratamento farmacológico , Argentina , Metotrexato , HistoplasmaRESUMO
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.
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Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Atenção à Saúde , Histoplasmose/epidemiologia , Patologistas , Infecções Oportunistas Relacionadas com a AIDS/complicações , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Adulto , Feminino , Guiana Francesa/epidemiologia , Histoplasmose/complicações , Histoplasmose/diagnóstico , Humanos , Masculino , Estudos RetrospectivosRESUMO
We aimed to describe the ways patients with disseminated histoplasmosis-a multifaceted and often lethal disease-present themselves and are explored. A retrospective, observational, multicentric study spanned the period between 1 January 1981 and 1 October 2014. Principal component analysis was performed for the sampling sites and for the clinical signs and symptoms. The factor loadings of the principal components were selected for eigenvalues > 1. The most frequent signs and symptoms were an alteration of the WHO general performance status, fever, digestive tract, respiratory signs and symptoms and lymphadenopathies. The most common sites sampled were bone marrow, respiratory tract, blood, lymph node and liver biopsies, with significant variations in the number of sites from which samples were taken to try to identify the pathogen. The principal component analysis clinical signs and symptoms leading to the diagnosis showed four main lines of variation. The factor loadings of the four main components were compatible with four broad types of clinical presentations and four types of exploration strategies. Extracting simple algorithms was difficult, emphasizing the importance of clinical expertise when diagnosis depends on obtaining a sample where Histoplasma can be seen or grown. Histoplasma antigen detection tests will help simplifying the algorithms.
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RESUMEN La histoplasmosis es una micosis profunda causada por el hongo dimorfo Histoplasma capsulatum (H. capsulatum). Ingresa al organismo principalmente por la vía inhalatoria en forma de microconidias, las cuales se transforman en elementos levaduriformes intracelulares, y luego se diseminan por vía hemática. La primoinfección en pacientes inmunocompetentes suele ser asintomática y de resolución espontánea, pero los pacientes inmunodeprimidos generalmente pueden presentar una enfermedad diseminada con compromiso mucocutáneo con pápulas, nódulos, gomas, úlceras de fondo granulomatoso serosanguinolento y costras. Se presenta un caso clínico de un paciente diabético inmunodeprimido con infección por H. capsulatum, en el cual se realiza diagnóstico a partir de las lesiones cutáneas.
SUMMARY Histoplasmosis is a deep mycosis caused by the dimorfo fungus Histoplasma capsulatum (H. capsulatum). Which enters the body mainly through the inhalation route in the form of microconidia which are transformed into intracellular levaduriform elements, and then disseminated by blood. The primary infection in immunocompetent patients is usually asymptomatic and spontaneously resolved, but immunocompromised patients can usually present with a disseminated disease with mucocutaneous involvement, with papules, nodules, gums, granulomatous serosanguinolent fundus ulcers and scabs. A clinical case of an immunocompromised diabetic patient with H. capsulatum infection is presented, in which diagnosis is made from the skin lesions.
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Introduction: Histoplasmosis is the main opportunistic infection and cause of death in HIV-infected persons living with HIV in French Guiana and probably in most of Latin America. The objective of the present study was to compare cutaneomucous histoplasmosis to non-cutaneomucous histoplasmosis in French Guiana. Methods: Between 1981 and 2014 AIDS-related disseminated histoplasmosis patients followed in the three hospitals of French Guiana were retrospectively studied. Only proven incident cases of histoplasmosis, either by pathology and/or mycological analysis, were considered. Mucocutaneous histoplasmosis was ascertained by a positive mucosal or cutaneous biopsy. Results: Thirty-one patients had mucocutaneous lesions, and 318 had no mucocutaneous lesions. Patients with cutaneomucous lesions were more likely to have had prior opportunistic infections (35.5%) than those who did not have cutaneomucous lesions (19.5%). They were more likely to be very severely immunocompromised (CD4 count < 50) (90.3% versus 62.8%) and less likely to have digestive signs (32.3% versus 74.1%) and superficial adenopathies (29% versus 50.2%) than those without cutaneomucous lesions. In terms of simple biological examinations, patients with cutaneomucous lesions had fewer signs of cholestasis. The diagnosis was significantly more likely to be performed by direct examination and pathology in those with cutaneomucous lesions than in those without such lesions. On the contrary, patients with cutaneomucous lesions were less likely to be diagnosed by fungal culture than those without cutaneomucous lesions. There was a greater but non-significant risk of early death in those with cutaneomucous lesions relative to those without (OR = 2.28 (95%CI = 0.83-5.7), p = 0.056. Conclusions: Mucocutaneous forms were associated with more profound immunosuppression and perhaps risk of early death. They are easily accessible for diagnosis.
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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.
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Infecções por Citomegalovirus/diagnóstico , Histoplasmose/sangue , Linfo-Histiocitose Hemofagocítica/diagnóstico , Antivirais/uso terapêutico , Infecções por HIV/complicações , Infecções por HIV/virologia , Histoplasmose/complicações , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Linfo-Histiocitose Hemofagocítica/etiologia , Linfo-Histiocitose Hemofagocítica/terapia , Masculino , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Disseminated histoplasmosis (DH) is an opportunistic fungal infection in severely immunocompromised patients with HIV infection. Haemophagocytic syndrome (HFS), which can occur in these co-infected patients when the immune response is significantly altered, is often associated with high mortality. AIMS: To describe the epidemiological, clinical, analytical and microbiological characteristics, along with studying the presence of HFS, in patients with DH-HIV. METHODS: A retrospective study was conducted on a case series using data from the clinical records of patients diagnosed with DH and HIV infection during the years 2014 and 2015. RESULTS: DH was diagnosed in 8 (1.3%) of 597 HIV patients. All patients were in stage C3, and 75% (6/8) were not receiving combined antiretroviral therapy (CART). The remaining two patients had recently begun CART (possible immune reconstitution syndrome). Five (62.5%) of the 8 patients met criteria for HFS. The most frequent clinical symptoms were lymphoproliferative and consumptive syndrome, respiratory compromise, and cytopenia. Histoplasma was isolated in lymph nodes of 75% (6/8) of the patients, in blood samples in 25% (2/8), and also in intestinal tissue in one patient. The antifungal therapy was amphotericin B deoxycholate, without adjuvants. The overall mortality was 50%. CONCLUSIONS: In this case series, DH-HIV co-infection frequently progressed to HFS with high mortality. The clinical picture may resemble that of other systemic opportunistic infections, such as tuberculosis, or can take place simultaneously with other infections. Clinical suspicion is important in patients with severe cytopenia and lymphoproliferative and consumptive syndrome in order to establish an early diagnosis and prescribing a timely specific therapy.
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Infecções por HIV/complicações , Histoplasmose/complicações , Linfo-Histiocitose Hemofagocítica/complicações , Adulto , Feminino , Hospitais , Humanos , Masculino , Pessoa de Meia-Idade , Peru , Estudos RetrospectivosRESUMO
Background: Disseminated histoplasmosis is a major killer of patients with advanced HIV. It is proteiform and often hard to diagnose in the absence of diagnostic tests. We aimed to describe disseminated histoplasmosis with lymphadenopathies in French Guiana and to compare survival and severity of those patients to patients without lymphadenopathies. Methods: A retrospective cohort study was performed on data records collected between January 1, 1981 and October 1, 2014. Results: Among 349 cases of disseminated histoplasmosis 168 (48.3%) had superficial lymphadenopathies and 133(38.1%) had deep lymphadenopathies. The median LDH concentration, ferritin concentration, TGO concentration, and WHO performance status were lower among patients with deep lymphadenopathies than those without deep lymphadenopathies. There was a significant decrease in the risk of early death (<1 month) among those with deep lymphadenopathies relative to those without (OR=0.26 (95%CI=0.10-0.60), P=0.0006) and in the overall risk of death (OR=0.33 (95%CI=0.20-0.55), P<0.0001). These associations remained strongly significant after adjusting for time period, CD4 counts, age, delay between beginning of symptoms and hospital admission, antifungal and antiretroviral treatment. Conclusions: The present data show that in patients with advanced HIV and disseminated histoplasmosis, the presence of deep lymphadenopathies is associated with fewer markers of severity and a lower risk of death. To our knowledge it is the first study to show this. The presence of deep lymphadenopathies is hypothesized to reflect the patient's partially effective defense against H. capsulatum.
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Infecções Oportunistas Relacionadas com a AIDS , Histoplasmose , Linfadenopatia , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Antifúngicos/uso terapêutico , Guiana Francesa , Histoplasma , Histoplasmose/complicações , Histoplasmose/diagnóstico , Histoplasmose/tratamento farmacológico , Humanos , Linfonodos , Linfadenopatia/tratamento farmacológico , Estudos RetrospectivosRESUMO
Resumen La histoplasmosis diseminada es una micosis sistémica endémica, causada por el hongo dimórfico Histoplasma capsulatum. Las manifestaciones clínicas dependen de la carga fúngica inhalada, del estado inmunológico del paciente y de la virulencia de la cepa infectante. La variante diseminada es más frecuente en inmunocomprometidos, registrándose 90% de los casos en pacientes con serología positiva para VIH. En esta serie se evaluaron 37 pacientes con diagnóstico de infección por VIH e histoplasmosis diseminada. El 43,2% de los pacientes no sabía su serología en forma previa a la consulta por histoplasmosis. Las principales manifestaciones clínicas fueron síndrome de impregnación (67,6%), fiebre (64,9%), síntomas respiratorios (62,2%) y manifestaciones muco-cutáneas (67,6%), entre otras. El 94,6% de los pacientes presentó anemia, 75,7% tenía bicitopenia y 32,4% pancitopenia. La sensibilidad de los hemocultivos fue de 70,4%. El 86,5% no tuvo otra infección oportunista concomitante al momento del diagnóstico. En 83,8% de los pacientes la histoplasmosis diseminada fue la primera enfermedad marcadora de SIDA. Se registró una mortalidad de 14,7%.
Disseminated histoplasmosis is an endemic systemic mycosis, caused by the dimorphic fungus Histoplasma capsulatum. The clinical manifestations depend on the inhaled fungal load, the immunological state of the patient and the virulence of the infecting fungal strain. The disseminated variant is most frequent in immunocompromised patients, with 90% of cases in patients with positive serology for HIV, In this series, 37 patients with diagnosis of HIV and disseminated histoplasmosis were evaluated. The 43.2% of the patients did not know their serology prior to the consultation due to histoplasmosis. The main clinical causes were impregnation syndrome (67.6%), fever (64.9%), respiratory symptoms (62.2%) and mucocutaneous manifestations (67.6%), among others. The 94.6% of the patients presented anemia, 75.7% had bicytopenia and 32.4% pancytopenia. The sensitivity of the blood cultures was 70.4%. The 86.5% of the patients did not have another opportunistic infection concomitant at the time of diagnosis. In 83.8% of patients, disseminated histoplasmosis was the first AIDS disease. A mortality of 14.7% was recorded.
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Humanos , Masculino , Feminino , Adulto , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Histoplasmose/diagnóstico , Estudos Retrospectivos , Hospedeiro Imunocomprometido , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Histoplasmose/tratamento farmacológicoRESUMO
Abstract The diagnosis of progressive disseminated histoplasmosis is often a challenge to clinicians, especially due to the low sensitivity and long turnaround time of the classic diagnostic methods. In recent years, studies involving a variety of non-culture-based diagnostic tests have been published in the literature. We performed a systematic review by selecting studies evaluating non-culture-based diagnostic methods for progressive disseminated histoplasmosis. We searched for articles evaluating detection of antibody, antigens, as well as DNA-based diagnostic methods. A comprehensive PUBMED, Web of Science, and Cochrane Library search was performed between the years 1956 and 2016. Case reports, review articles, non-human models and series involving less than 10 patients were excluded. We found 278 articles and after initial review 18 articles were included: (12) involved antigen detection methods, (4) molecular methods, and (2) antibody detection methods. Here we demonstrate that the pursuit of new technologies is ultimately required for the early and accurate diagnosis of disseminated histoplasmosis. In particular, urinary antigen detection was the most accurate tool when compared with other diagnostic techniques.
Assuntos
Humanos , Testes Sorológicos/métodos , Técnicas Imunoenzimáticas/métodos , Histoplasmose/diagnóstico , Reação em Cadeia da Polimerase/métodos , Sensibilidade e EspecificidadeRESUMO
The diagnosis of progressive disseminated histoplasmosis is often a challenge to clinicians, especially due to the low sensitivity and long turnaround time of the classic diagnostic methods. In recent years, studies involving a variety of non-culture-based diagnostic tests have been published in the literature. We performed a systematic review by selecting studies evaluating non-culture-based diagnostic methods for progressive disseminated histoplasmosis. We searched for articles evaluating detection of antibody, antigens, as well as DNA-based diagnostic methods. A comprehensive PUBMED, Web of Science, and Cochrane Library search was performed between the years 1956 and 2016. Case reports, review articles, non-human models and series involving less than 10 patients were excluded. We found 278 articles and after initial review 18 articles were included: (12) involved antigen detection methods, (4) molecular methods, and (2) antibody detection methods. Here we demonstrate that the pursuit of new technologies is ultimately required for the early and accurate diagnosis of disseminated histoplasmosis. In particular, urinary antigen detection was the most accurate tool when compared with other diagnostic techniques.