Riesgo de mortalidad en infecciones invasoras por Fusarium spp en niños con enfermedades hemato-oncológicas: una revisión sistemática de la literatura / Risk of mortality in invasive infections by Fusarium spp in children with hematooncological diseases: a literature systematic review

INTRODUCCIÓN: Los estudios sobre la infección fúngica invasora (IFI) por Fusarium spp en pacientes pediátricos con patología hemato-oncológica, son escasos, correspondiendo en general a series clínicas descriptas en forma retrospectiva, lo que dificulta conocer en profundidad sus características y evolución. OBJETIVO: Analizar la evolución fatal de la IFI causada por Fusarium spp en pacientes pediátricos con patología hemato-oncológica, llevándose a cabo una revisión sistemática. MATERIAL Y MÉTODOS: La búsqueda bibliográfica se realizó con fecha 23 de marzo de 2023, en las principales bases de datos (Medline (a través de PubMed), Embase (a través de Embase-Elsevier), The Cochrane Library (a través de Wiley), Cinahl (a través de EbscoHOST), SCI-EXPANDED y Scielo (a través de la WOS) y Scopus (a través de Scopus-Elsevier) y libre (mediante el motor Google) y revisando las citas de los artículos incluidos. RESULTADOS: Se rescataron 1.341 artículos, de los cuales se descartaron 931 por diversas razones. Mediante el análisis de los textos completos, finalmente se incluyeron 11 estudios. Todos los estudios eran de nivel 4 (serie de casos). Se detectó una notoria heterogeneidad (p < 0,008) entre los mismos. La mediana de la frecuencia de muerte observada implicó a un tercio de los afectados (Md 33 %; Q1:22,7-Q4:75). CONCLUSIONES: La mortalidad por IFI por Fusarium spp fue alta en niños con patología hemato-oncológica, en especial en aquellos con neutropenia profunda y mala respuesta al tratamiento de su enfermedad de base

BACKGROUND: Studies on invasive fungal infection (IFI) by Fusarium spp in pediatric patients with hemato-oncological pathology are scarce and limited and a few series of cases described retrospectively, which makes it difficult to fully understand their characteristics and outcome. With the aim of analyzing the fatal evolution of these patients, this systematic review was carried out. METHODS: The literature search was performed up to March 23, 2023, in the main databases, as Medline (through PubMed), Embase (through Embase-Elsevier), The Cochrane Library (through Wiley), Cinahl (through EbscoHOST), SCI-EXPANDED and Scielo (through WOS) and Scopus (through Scopus-Elsevier) and free (through the Google engine) and reviewing the citations of the included articles. RESULTS: 1341 articles were retrieved, of which 931 were discarded for various reasons. By analyzing its full texts, 11 studies were finally included. It was observed that heterogeneity among them was relevant (p < 0.008). Median frequency of death involved one third of those affected (Md 33%; Q1:22,7-Q4:75). CONCLUSIONS: Mortality due to IFI due to Fusarium spp was high in children with hemato-oncological pathology, especially in those with severe neutropenia and poor response to treatment of their underlying disease.

Assessment of genotyping markers in the molecular characterization of a population of clinical isolates of Fusarium in Colombia / Evaluación de marcadores de genotipificación en la caracterización molecular de una población de aislamientos clínicos de Fusarium en Colombia

Introduction: Fusarium is a very heterogeneous group of fungi, difficult to classify, with a wide range of living styles, acting as saprophytes, parasites of plants, or pathogens for humans and animals. Prevalence of clinical fusariosis and lack of effective treatments have increased the interest in the precise diagnosis, which implies a molecular characterization of Fusarium populations. Objective: We compared different genotyping markers in their assessment of the genetic variability and molecular identification of clinical isolates of Fusarium. Materials and methods: We evaluated the performance of the fingerprinting produced by two random primers: M13, which amplifies a minisatellite sequence, and (GACA)4, which corresponds to a simple repetitive DNA sequence. Using the Hunter Gaston Discriminatory Index (HGDI), an analysis of molecular variance (AMOVA), and a Mantel test, the resolution of these markers was compared to the reference sequencing-based and PCR genotyping methods. Results: The highest HGDI value was associated with the M13 marker followed by (GACA)4. AMOVA and the Mantel tests supported a strong correlation between the M13 classification and the reference method given by the partial sequencing of the transcription elongation factor 1-alpha (TEF1-α) and rDNA 28S. Conclusion: The strong correlation between the M13 classification and the sequencing-based reference together with its higher resolution demonstrates its adequacy for the characterization of Fusarium populations.

Introducción. Fusarium es un grupo heterogéneo de hongos, difícil de clasificar y con una amplia gama de estilos de vida, que actúa como saprófito, parásito de plantas o patógeno de humanos y animales. La prevalencia de la fusariosis clínica y la falta de tratamientos han incrementado el interés en su diagnóstico preciso, lo que conlleva la caracterización molecular de las poblaciones. Objetivo. Comparar marcadores de genotipificación en la evaluación de la variabilidad genética e identificación de aislamientos clínicos de Fusarium. Materiales y métodos. Se evaluó la huella genética producida por dos cebadores aleatorios: M13, que amplifica una secuencia minisatélite, y (GACA)4, que corresponde a una secuencia repetitiva de ADN. Utilizando el índice discriminatorio de Hunter Gaston (HGDI), el análisis de varianza molecular (AMOVA) y una prueba de Mantel, se comparó la resolución de estos marcadores con métodos de genotipificación basados en secuenciación y PCR. Resultados. El mayor HGDI se asoció con el marcador M13, seguido de (GACA)4. Las pruebas AMOVA y Mantel mostraron correlación entre las clasificaciones obtenidas con M13 y la referencia basada en la secuenciación parcial del factor de elongación de transcripción 1-alfa (TEF1-α) y el ADNr 28S. Conclusión. La fuerte correlación entre la clasificación obtenida con M13 y el método de referencia, así como su alta resolución, demuestran su idoneidad para la caracterización de poblaciones de Fusarium.

Multisystemic fusariosis with fulminant evolution

Abstract This report presents the case of a 13-year-old female patient with history of acute myeloid leukemia, who, after a bone marrow transplant, began to vomit and experienced rapidly progressive deterioration of consciousness, in addition to disseminated erythematous-violaceous macules, and some blisters with hemorrhagic content inside. Skin biopsy evidenced intravascular filamentous structures. A blood culture confirmed the presence of Fusarium oxysporum. Intravenous treatment with voriconazole was initiated. The patient evolved unfavorably with multiple necrotic skin lesions, ischemic brain lesions, and death.

Disseminated fusariosis in a patient with bone marrow aplasia

Abstract Fusariosis is a superficial or systemic infection, which occurs mainly in immunocompromised hosts, especially in patients with hematological neoplasia; 70%-75% of the cases present cutaneous manifestations. The disseminated form is rare and difficult to diagnose; even with specific treatment, the evolution is usually fatal. Currently, it is considered an emerging disease; in some centers, it is the second most common cause of invasive mycosis, after aspergillosis. The authors describe a case of a female patient with idiopathic bone marrow aplasia and disseminated fusariosis, who initially appeared to benefit from voriconazole and amphotericin B; however, due to persistent neutropenia, her clinical condition deteriorated with fatal evolution.

Human fusariosis: An emerging infection that is difficult to treat

Abstract Fusarium spp. has been associated with a broad spectrum of emerging infections collectively termed fusariosis. This review includes articles published between 2005 and 2018 that describe the characteristics, clinical management, incidence, and emergence of these fungal infections. Fusarium solani and F. oxysporum are globally distributed and represent the most common complexes. Few therapeutic options exist due to intrinsic resistance, especially for the treatment of invasive fusariosis. Therefore, the use of drug combinations could be an important alternative for systemic antifungal resistance. Increase in the number of case reports on invasive fusariosis between 2005 and 2018 is evidence of the emergence of this fungal infection.

Disseminated fusariosis with cutaneous involvement in hematologic malignancies: report of six cases with high mortality rate

Abstract: Fusariosis is due to inhalation or direct contact with conidia. Clinical presentation depends on host's immunity and can be localized, focally invasive or disseminated. Given the severity of this infection and the possibility for the dermatologist to make an early diagnosis, we report six cases of patients with hematologic malignancies, who developed febrile neutropenia an skin lesions suggestive of cutaneous fusariosis. All patients had skin cultures showing growth of Fusarium solani complex, and they received amphotericin B and voriconazole. As this infection can quickly lead to death, dermatologists play a crucial role in diagnosing this disease.

Fusariosis invasiva: reporte de tres casos en Perú / Invasive Fusariosis: Report of Three Cases in Peru

RESUMEN Las especies de Fusarium son un grupo de hongos que causan infecciones superficiales, localmente invasivas y enfermedad diseminada, que ocurren principalmente en huéspedes inmunocomprometidos, y ocasionalmente en individuos inmunocompetentes. Presentamos tres casos que ponen en manifiesto tres diferentes formas clínicas de la enfermedad por Fusarium spp., que afectaron diversos tipos de pacientes (pacientes con malignidad hematológica, enfermedad renal crónica en diálisis peritoneal y post-quirúrgico por patología osteoarticular), cada una con características propias que ameritan su discusión. Estos casos ponen de manifiesto diferentes formas clínicas de fusariosis invasiva causadas por especies del complejo Fusarium solani en pacientes con diferentes patologías y manejo terapéutico que podrían ser factores de riesgo para el desarrollo de la enfermedad. El reconocimiento clínico de la Fusariosis, no solo en pacientes oncohematólogicos, junto con un diagnóstico y tratamiento oportuno contribuyen al éxito del tratamiento y a una reducción en la mortalidad.

ABSTRACT Fusarium species are a group of fungi that cause superficial infections, locally invasive and disseminated disease, which occur mainly in immunocompromised hosts, and occasionally in immunocompetent individuals. We present three cases that show three different clinical forms of Fusarium spp. disease that affected different types of patients (patients with hematological malignancy, chronic kidney disease in peritoneal dialysis and post-surgical for osteoarticular pathology), each with its own characteristics that merit discussion. These cases show different clinical forms of invasive fusariosis caused by Fusarium solani complex species in patients with different pathologies and therapeutic management that could be risk factors for the development of the disease. The clinical recognition of fusariosis, not only in oncohematological patients, together with a timely diagnosis and treatment contribute to the success of the treatment and a reduction in mortality.

Tratamiento exitoso de una fusariosis diseminada en un paciente neutropénico febril con terapia antifúngica combinada de voriconazol más anfotericina B deoxicolato / Successful treatment of disseminated fusariosis in a febrile neutropenic patient with combined antifungal therapy of voriconazol plus amphotericin B deoxycholate

Resumen Presentamos el caso clínico de un paciente con una leucemia linfoblástica aguda (LLA) que desarrolló una fusariosis diseminada por Fusarium verticillioides durante un episodio prolongado de neutropenia febril post quimioterapia. Fue exitosamente tratado cuando se usó terapia combinada de voriconazol más anfotericina B deoxicolato.

We report a case of a patient with acute lymphoblastic leukemia (ALL), who developed a disseminated infection by Fusarium verticillioides during chemotherapy-induced neutropenia. He was successfully treated only after combination therapy with voriconazole plus amphotericin B deoxycolate was used, but not when these compounds were used in an isolated form.

Trasplante de médula ósea alogénico en un paciente con fusariosis diseminada y leucemia mieloide aguda / Allogeneic hematopoietic cell transplantation in a patient with disseminated fusariosis and acute myeloid leukemia

La infección diseminada por Fusarium se ha convertido en un problema creciente en las personas con neoplasias hematológicas malignas, principalmente en pacientes con leucemias agudas; se describen cada vez más casos en aquellos sometidos a un trasplante de médula ósea. No existe un tratamiento óptimo establecido para la fusariosis diseminada. La mortalidad global comunicada de esta infección oscila entre el 50 y el 80%. Se presenta a continuación el caso de un paciente de sexo masculino de 29 años, con diagnóstico de leucemia mieloide aguda, que presenta como complicación una fusariosis diseminada, y logra sobrellevar un trasplante alogénico de médula ósea en el Hospital Italiano de San Justo (Argentina) de forma exitosa. (AU)

Disseminated fusariosis has become an increasing problem in people with hematopoietic neoplasms, mainly in patients affected by acute leukemias, and even more in those who undergo hematopoietic cell transplantation. There is not an optimal treatment for disseminated fusariosis. The global mortality described in the literature is between 50% and 80%. We introduce a case of a 29 year old patient with diagnosis of acute myeloid leukemia complicated with disseminated fusariosis, who copes with an allogeneic hematopoietic cell transplantation with a successful outcome in the "Hospital Italiano de San Justo" (Argentina). (AU)

Diversidad genética de aislamientos de Fusarium graminearum sensu lato asociados con la fusariosis de la espiga en trigo de diversas localidades argentinas / Genetic diversity of Fusarium graminearum sensu lato isolates from wheat associated with Fusarium Head Blight in diverse geographic locations of Argentina

La fusariosis de la espiga de trigo es una importante enfermedad para la región pampeana Argentina; Fusarium graminearum es el principal patógeno asociado. Se estudió el polimorfismo del ADN de un conjunto de aislamientos utilizando las técnicas de IGS-RFLP e ISSR. La técnica de IGS-RFLP produjo 41 bandas, 30 de ellas fueron polimórficas. El análisis de los ISSR mostró 87 bandas con 47 bandas polimórficas. La primera de estas metodologías fue más eficiente, ya que detectó mayor promedio polimórfico (59,91%) que la segunda (44,11%). Los valores promedio del contenido de información polimórfica (PIC) fueron 0,211 y 0,129, respectivamente. Se identificaron 20 haplotipos por IGS-RFLP, mientras que el análisis de los ISSR reveló 15 haplotipos. La agrupación de genotipos obtenida en ambos dendrogramas fue diferente. Los grupos genéticos obtenidos por la técnica de IGS-RFLP mostraron una asociación parcial con el origen geográfico. Este es el primer reporte que analiza la variabilidad genética en poblaciones de F. graminearum de trigo empleando marcadores IGS-RFLP e ISSR en Argentina

Fusarium Head Blight is an important wheat disease in the Argentine Pampas region, being Fusarium graminearum the predominant pathogen. DNA polymorphism of the isolates was analyzed by IGS-RFLP and ISSR. IGS-RFLP and ISSR profiling were carried out using six endonucleases and eight primers, respectively. IGS-RFLP yielded 41 bands, 30 of which were polymorphic while ISSR produced 87 bands with 47 polymorphic bands. Both markers showed genetic variability among the analyzed isolates; however, IGS-RFLP was more efficient than ISSR, showing a higher polymorphic average (59.91%) than the latter (44.11%). The averages of polymorphic information content (PIC) were 0.211 and 0.129, respectively. Twenty haplotypes were identified by IGS-RFLP and 15 haplotypes by ISSR. Genotype clustering within dendrograms was different for both types of markers. The genetic groups obtained by IGS-RFLP showed a partial association to geographic origin. This is the first report on genetic variability of F. graminearum isolates from wheat in Argentina using IGS-RFLP and ISSR markers

Probable fusariosis diseminada en pacientes con malignidades hematológicas / Probable disseminated fusariosis in patients with hematologic malignancies

Se describen dos casos de Probable Fusariosis Diseminada (PFD) en pacientes con malignidades hematológicas atendidos en el Hospital Médico-Quirúrgico y Oncológico del ISSS (HMQ-O-ISSS). El caso 1 presentó una respuesta satisfactoria al tratamiento con Voriconazole, mientras que el caso 2 a pesar del tratamiento temprano con Voriconazole falleció. En ambos casos no logró aislarse el hongo en hemocultivos, pero si se logró visualizar en el estudio histopatológico. Fusariosis diseminada debe ser tomada en cuenta en el diagnóstico diferencial de infecciones fúngicas invasivas que se presentan en pacientes con malignidades hematológicas. Para nuestro conocimiento son los primeros casos reportados en El Salvador

We described two cases of Probable Disseminated Fusariosis in patients with hematological neoplasms who were being treated at the HMQ-O-ISSS. The first case had satisfactory response to treatment with Voriconazol, while case 2 died despite early Voriconazol treatment. In both cases, we failed to isolate fungus in blood cultures, but it was displayed on histopathology. Disseminated Fusariosis should be taken into account in the differential diagnosis of invasive fungal infections that appear in patients with hematologic malignancies. For our knowledge, these are the first two cases reported in El Salvador

Disseminated fusariosis in a patient with acute lymphoblastic leukaemia: A case report and literature review

Fusarium spp are molds found in the soil and may be saprophytic or fa c u l t a t ive plant p a t h ogens. These are rare but important opportunistic pathogens in immunocompromised patients especially those with hematologic malignancies. Fusarium spp usually cause local infections such as onychomycosis and infections of surgical and burn wound. However more importantly, these pathogens can lead to severe disseminated infection with invo l vement of multiple organs including skin. This disseminated form of fusariosis occurs exclusively in patients with prolonged, severe neutropaenia especially in patients with acute leukaemia or those u n d e rgoing bone marrow transplantation. Prognosis of disseminated fusariosis is usually guarded if not recognized early. We report a rare case of disseminated fusariosis in a patient with acute lymphoblastic leukaemia.

Efeito de extratos vegetais no controle de Fusarium oxysporum f. sp tracheiphilum em sementes de caupi / Effect of naturals extracts on the control of Fusarium oxysporum f. sp tracheiphilum in cowpea seeds

A fusariose é uma doença de grande importância para a cultura do feijoeiro em virtude da redução da produtividade. O controle da doença vem sendo realizado com aplicações indiscriminadas de fungicidas químicos, acarretando problemas ao homem e ao meio ambiente. Objetivou-se, no presente trabalho, avaliar o efeito de extratos vegetais no controle de Fusarium oxysporum f. sp tracheiphilum, proveniente de sementes de caupi, comparando-se com o efeito do fungicida químico. Utilizaram-se extratos de alho, angico e manjericão, isolados ou combinados entre si e ou em associação ao fungicida Mancozeb. Uma alíquota de 50 µL de cada tratamento foi adicionada em orifício feito no centro das placas de Petri com BDA, sobre o qual depositou-se um disco de micélio do fungo. Avaliou-se durante sete dias, medindo-se o crescimento micelial do patógeno. Sementes de caupi foram desinfestadas com hipoclorito de sódio a 4,0%, semeadas em sacos de polietileno contendo solo autoclavado. Oito dias após germinação, efetuaram-se ferimentos no colo das plântulas, aplicando-se suspensão de esporos do fungo (1,4 x 10-5 con/mL). As avaliações de severidade da doença foram realizadas diariamente durante 30 dias após a inoculação, utilizando-se escala de notas. Os extratos combinados de alho + manjericão e angico + manjericão não inibiram o crescimento micelial do fungo, enquanto o extrato de manjericão isoladamente, proporcionou o menor crescimento micelial, indicando a ação fungicida e inibitória desse tratamento sobre o fungo F. oxysporum f. sp tracheiphilum nas condições analisadas. O fungicida Mancozeb + o extrato de angico proporcionou menor média de severidade nas plantas avaliadas.

Wilt caused by Fusarium sp. in cowpea crop is a disease of great importance because it causes yield decrease. The control of this disease has been accomplished with uncontrolled applications of chemical fungicides causing problems for humans and environment. The present work had the objective to compare the effect of natural extracts on the control of Fusarium oxysporum f. sp tracheiphlum, originated from seeds of cowpea (Vigna unguiculata L), compared to chemical fungicide effect. Extracts of Allium sativum, Anadenanthera colubrine, and Ocimum basilicum were used alone or in combination with Mancozeb. A 50 µL aliquot of each treatment was added in a hole (6 mm of diameter) made in the center of Petri dishes with BDA and a fungus mycelia disk was inoculated on it. Evaluations were done during seven days, measuring the pathogen mycelial growth. Seeds of cowpea were disinfected with sodium hypochlorite, sowed in plastic bags with autoclaved soil. Eight days after germination, wounds were made on the basal part of the plantlets, and fungus spore suspension (1.4 x 10-5 con/mL) was applied on it. Evaluations of the disease severity were accomplished daily during 30 days after inoculation, using a disease index. Combination of extracts of A. sativum + Ocimum basilicum and Anadenanthera colubrina + Ocimum basilicum did not reduce fungus mycelial growth, whereas Ocimum basilicum extract alone showed minor mycelial growth, indicating fungicide action of this treatment on F. oxysporum f. sp tracheipphlum under the conditions studied. Combination of Mancozeb + Anadenanthera colubrina was responsible for lower average of severity on the evaluated plants.

Successful Treatment of Disseminated Fusariosis with Liposomal Amphotericin B and Voriconazole in a Child Undergoing Chemotherapy / 대한소아혈액종양학회지

Fusarium species are common soil saprophytes and plant pathogens. In humans, several species have been recognized as agents of superficial infections. Disseminated Fusariosis have been increasingly described in immunocompromised patients, especially in neutropenic patients. The prognosis is very poor despites antifungal therapy. This is the report of Fusarium oxysporum infection in a 6-year-old patient with relapsed acute leukemia and prolonged neutropenia. The patient presented with persistent fever and multiple erythematous papules with central necrosis or vesicle. Fuasrium oxysporum was isolated and cultured from a skin biopsy specimen. Initially, the patient failed to respond to conventional amphotericin B but recovered after treatment was switched to liposomal amphotericin B and voriconazole.

A Case of Disseminated Fusarium Infection Treated by Liposomal Amphotericin B in a Leukemic Patient / 감염과화학요법

Fusarium spp., basically a superficial pathogen, is a newly emerging fungal pathogen of opportunistic infections in immunocompromised patients. At present, although Fusarium spp. are relatively resistant to amphotericin B, the combination of amphotericin B and surgical debridement appear to be optimal treatment for disseminated infection. Recently we experienced a 32-year-old neutropenic patient after induction chemotherapy for acute myelocytic leukemia presented with skin lesions and infiltrations in both lungs. We diagnosed with disseminated fusariosis by skin culture and successfully treated the patient with liposomal amphotericin B. We emphasize a high index of suspicion for skin lesions especially in immunocopromised patients.

A Case of Disseminated Fusarium Infection Treated by Liposomal Amphotericin B in a Leukemic Patient / 감염과화학요법

Fusarium spp., basically a superficial pathogen, is a newly emerging fungal pathogen of opportunistic infections in immunocompromised patients. At present, although Fusarium spp. are relatively resistant to amphotericin B, the combination of amphotericin B and surgical debridement appear to be optimal treatment for disseminated infection. Recently we experienced a 32-year-old neutropenic patient after induction chemotherapy for acute myelocytic leukemia presented with skin lesions and infiltrations in both lungs. We diagnosed with disseminated fusariosis by skin culture and successfully treated the patient with liposomal amphotericin B. We emphasize a high index of suspicion for skin lesions especially in immunocopromised patients.