Fungal Infections In Children Research Articles

Invasive Fungal Infections in Children with Acute Leukemia: Epidemiology, Risk Factors, and Outcome.

Invasive fungal infections (IFI) cause morbidity and mortality in children with acute leukemia (AL). We retrospectively collected data on febrile neutropenic episodes (FNE) in AL children (2016-2021) and assessed factors associated with proven/probable IFI. Ninety-three children developed 339 FNE. Seventeen (18.3%) children developed 19 proven/probable IFI (11 yeast; eight molds). The proven/probable yeast IFI rate was 6/52 (11.5%) in children who belong to the high risk for IFI category (HR-IFI-AL: high-risk acute lymphocytic leukemia (ALL), acute myeloid leukemia, relapse); and 5/41 (12.2%) in the non-HR-IFI-AL category (standard/intermediate risk ALL). The proven/probable mold IFI rate was 7/52 (13.5%) in HR-IFI-AL children and 1/41 (2.4%) in the non-HR-IFI-AL category. In the multivariable analysis, underlying genetic syndrome, oral mucositis, and older age were significantly associated with proven/probable IFI, while a longer time since AL diagnosis was protective. Two of 13 (15.4%) HR-IFI-AL children died because of IFI. The elevated risks of proven/probable mold IFI and the associated mortality in HR-IFI-AL children, and high risk of invasive candidiasis in the non-HR-IFI-AL group, emphasize the need for the close monitoring of local epidemiology and the adjustment of practices accordingly.

Invasive fungal disease in children with viral pneumonia in pediatric intensive care unit in a tertiary care center from Eastern India

Background: Invasive fungal disease is common in immunocompromised children, although rare in children suffering from viral pneumonia. Recently, it was our observation that a large number of children who were otherwise normal were suffering from invasive fungal disease along with viral pneumonia. The aim of our study is to determine the epidemiological and clinical profile of fungal infection in children suffering from viral pneumonia. Subjects and Methods: It was a retrospective study of medical records of children between January 2023 and March 2023 from pediatric intensive care unit (PICU) tertiary care hospital from Eastern India. Children with suspected fungal disease as per inclusion criteria were included in the study. A total of 27 patients were enrolled in this study. The serum galactomannan and beta-D-glucan (BDG) were measured. Clinical profile and outcome were compared between children with and without invasive fungal disease. Results: Out of 27 subjects, 16 (59%) had invasive fungal disease. All had adenovirus pneumonia. Seven (4.44%) had acute respiratory distress syndrome while four (25%) had shock and multiple organ dysfunction syndrome each. The duration of mechanical ventilation (P = 0.01), duration of PICU stay (P = 0.02), and duration of hospital stay (P = 0.004) were significantly higher in children with invasive fungal disease. These children had significantly higher rates of complications (P = 0.001) and higher mortality (P = 0.04). Conclusions: The serum galactomannan and BDG can diagnose invasive fungal disease in patients of viral pneumonia with persistent symptoms for more than 2 weeks. The invasive fungal disease is associated with higher morbidity and mortality in these children.

Invasive fungal infections in children with leukemia in a tertiary hospital in Oman: An eight-year review.

Invasive fungal disease (IFD) is a common and serious consequence of leukemia in children and the incidence of these infections has increased due to chemotherapy. This study aimed to present the epidemiology of IFD in a cohort of children with leukemia from a tertiary reference institution in Oman. A retrospective study of IFDs in pediatric patients below 13 years of age with newly diagnosed or relapsed leukemia was conducted at the Royal Hospital in Muscat, Oman. From 2010 to 2017, IFD episodes in children with leukemia were evaluated retrospectively, considering age, gender, type of leukemia, chemotherapy regimen, IFD detection phase, neutropenia, prevention, diagnostic method, and treatment. Between 2010 and 2017, 198 children with leukemia were admitted and treated at Royal Hospital. Invasive fungal infection (IFI) was diagnosed in 32 patients out of 198 (16.1%), and IFI was defined as probable and proven in 53% (n=17) and 47% (n=15) of the cases, respectively. At 1.1:1, the male-to-female ratio was roughly equal. According to chest computed tomography scans, 65.6% of patients had radiological features of fungal infections. Positive fungal cultures were found in the bronchoalveolar lavage of three patients, 37.5% of whom had positive blood cultures, and 3% had positive urine cultures as a neonatal invasive candidiasis. In three patients, invasive aspergillosis caused pulmonary IFD, accounting for 9.3% of all infection sites. Candidaemia was found in 28% of IFD patients, and the most common organism was Candida tropicalis (15.6%), followed by Candida parapsilosis (6.25%). Furthermore, the major risk factor was febrile neutropenia. In children with leukemia, invasive fungal infection is common and serious. Despite aggressive treatment, mortality among these high-risk patients remains high.

Invasive Fungal Infections in Children With Acute Myeloid Leukemia: A Single-center Experience Over 19 Years.

Invasive fungal infections (IFIs) remain a significant cause of morbidity and mortality in children with acute myeloid leukemia (AML). This study aimed to evaluate the incidence, risk factors, etiology, and outcome of IFIs in children with AML and the effect of mold-active antifungal prophylaxis. We retrospectively reviewed pediatric patients treated for AML between January 2004 and December 2022. Proven, probable, or possible IFIs were defined using standardized definitions of the European Organization for the Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) classification published at 2008. A total of 298 febrile neutropenia episodes from 78 patients were evaluated. Proven, probable, and possible IFI rates were 3%, 2.6%, and 9.4%, respectively. Profound neutropenia was detected in 18 (58%) and prolonged neutropenia in 20 (64.5%) of the IFI episodes.. Invasive aspergillosis accounted for the majority of IFI episodes; however, non-albicans Candida spp. were the most isolated pathogens in the proven group. Patients with relapsed AML were particularly at risk for the development of IFI ( P =0.02). A significant decrease in IFI episodes was achieved with mold-active antifungal prophylaxis with voriconazole ( P =0.01, odds ratio: 0.288, %95 CI:0.104-0.797). The overall mortality was 35.8%, and the IFI-attributable mortality rate was 25%. In the multivariate analysis, relapsed disease was the most significant risk factor associated with mortality ( P =0.006, odds ratio:4.745; 95% CI: 1.573-14.316). Mold-active prophylaxis reduced the rate of IFIs in this cohort however IFI-related mortality was still high as 25% in pediatric AML patients. Relapsed AML was the most significant risk factor associated with mortality.

Nonculture Diagnostics in Invasive Fungal Infections in Children.

Nonculture Diagnostics in Invasive Fungal Infections in Children.

Rising burden of superficial fungal infections in India and the role of Clotrimazole for optimal management

Cutaneous dermatophytosis are among the most common infections seen in clinical practice. Over the past few years there has been a rising trend in the prevalence with change in spectrum of infection and isolation of some uncommon species. Recognition and appropriate treatment of these infections is important to reduce the morbidity and discomfort and also reduce the possibility of transmission. Azoles are the antifungal agents used extensively to treat dermatophytosis. Clotrimazole is mainly used locally in the treatment of skin fungal infections due to dermatophytes and yeasts. It is known to provide a broad-spectrum antifungal coverage against dermatophytes, moulds, yeasts and some bacteria, and is an efficient, safe and well accepted treatment for skin fungal infections in children and adults. This review provides an overview of the role of topical clotrimazole available as cream and powder and in combination with topical steroid for the optimal management of skin fungal infections.

New Perspectives on Primary Prophylaxis of Invasive Fungal Infection in Children Undergoing Hematopoietic Stem Cell Transplantation: A 10-Year Retrospective Cohort Study

Allogenic hematopoietic stem cell transplantation (a-HCT) remains a therapeutic treatment for many pediatric hematological diseases. The occurrence of invasive fungal infections (IFIs) is a complication for which ECIL-8 recommends primary antifungal prophylaxis. In this study, we evaluated the impact of our local strategy of not systematically administering primary antifungal prophylaxis in children undergoing a-HCT on the occurrence and mortality of IFIs. We performed a retrospective monocentric study from 2010 to 2020. We retained all proven and probable IFIs diagnosed during the first year post a-HCT. 308 patients were included. Eighteen patients developed twenty IFIs (thirteen proven, seven probable) (6.5%) among which aspergillosis (n = 10, 50%) and candidosis (n = 7, 35%) were the most frequently diagnosed infections. Only 2% of children died because of an IFI, which represents 14% of all deaths. Multivariate analysis found that age > 10 years (OR: 0.29), the use of a therapeutic antiviral treatment (OR: 2.71) and a low neutrophil count reconstitution (OR: 0.93) were significantly associated with the risk of IFI occurrence. There was also a trend of malignant underlying disease and status ≥ CR2 but it was not retained in multivariate analysis. IFI occurrence was not higher in our cohort than what is reported in the literature with the use of systematic antifungal prophylaxis, with a good survival rate nonetheless. Thus, a prophylaxis could be considered for children with a high risk of IFI such as those aged over 10 years.

A Practical Guide to Antifungal Susceptibility Testing.

We review antifungal susceptibility testing and the development of clinical breakpoints, and detail an approach to using antifungal susceptibility results when breakpoints have not been defined. This information may prove helpful when selecting therapy for invasive fungal infections in children.

Management and outcomes of intracranial fungal infections in children and adults in Africa: a scoping review protocol

IntroductionThe protocol presents the methodology of a scoping review that aims to synthesise contemporary evidence on the management and outcomes of intracranial fungal infections in Africa.Methods and analysisThe scoping review...

Neonatal-Onset Inflammatory Tinea Capitis by Microsporum canis Due to a Woolen Hat.

Tinea capitis is a common fungal infection in children, but it is rare in newborns. We report a case of a 3-week-old infant presenting with scalp annular erythema. She had a history of wearing a woolen hat one week before the disease onset. Wood's lamp and dermoscopic findings favoured the diagnosis of tinea capitis. Further examinations of her scalp, including direct KOH examination and fungal culture confirmed the diagnosis of tinea capitis caused by treatment with oral griseofulvin was effective. Neonatal tinea capitis is often misdiagnosed due to its rarity and atypical presentation. A thorough history (including the contacting history of clothes made of animal fur), physical examination and further mycological examinations are required for diagnosis. Griseofulvin, itraconazole and fluconazole have been reported to be effective drugs for the treatment of children tinea capitis. Liver enzymes should be regularly monitored during the period of using antifungal agents.

Investigating the effect of sodium chloride on the prevention of mucormycosis fungal infection in children with acute lymphocytic leukemia during treatment

Background: Given that no comprehensive study was conducted regarding the effect of sodium chloride on the prevention of mucormycosis fungal infection in acute leukemia patients during treatment, this study aimed the investigating the effect of sodium chloride  on the prevention of mucormycosis fungal infection in acute lymphocytic leukemia patients during treatment.
 Materials and Methods: This retrospective study was conducted on children with ALL who were undergoing chemotherapy in the induction phase and were susceptible to fungal and infectious diseases. Then 84 patients were randomly divided into the two groups. One group (n=46) received nasal drop containing sodium chloride (NORMONIX, 0.65%, three times a day) as the intervention group during treatment and another group did not receive sodium chloride (control group)(n=38). If the symptoms of mucormycosis was observed and detected (positive test), the injection of amphotrypsin B was started.
 Results: In the current study, 84 patients entered the study.  The mean age of patients in the control group and the intervention group was 7.84±3.45, and 6.45±3.4 years, respectively (P>0.05). Positive mucormycosis was seen in 24 (63.2%) patients in the control group and 16 (34.78%) patients in the intervention group (P=0.01).
 Conclusion: According to the findings of this study, the frequency of patients with positive mucormycosis in the NaCl group was significantly lower than the control group.  Therefore, it seems that NaCl drop can be effective regarding reducing the incidence of mucormycosis fungal infection and can decrease the need to amphotrypsin B, but further studies should be conducted in this regard.

Role of Antifungal Prophylaxis in Invasive Fungal Infection in Children with Acute Lymphoblastic Leukemia—A Retrospective Cross-Sectional Study

AbstractIntroduction Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Its outcome in India is not as good as that in the western world. One of the important reasons for lesser survival rates is opportunistic infections, including invasive fungal infections (IFIs). Antifungal prophylaxis (AFP) in ALL children is routinely not followed. However, owing to its incidence in high-risk ALL, this study is focused on the use of AFP in those children.Objectives This retrospective study investigated the role of AFP in newly diagnosed children with high-risk ALL on intensive blocks of therapy on regimens B and C of the United Kingdom Acute Lymphoblastic Leukemia 2003 protocol.Materials and Methods The study was conducted in a tertiary care center from 1st December 2013 to 31st December 2019 and included children with ALL from 1 to 18 years of age. Routine AFP with voriconazole was commenced for high-risk ALL children from 1st July 2017 onward in our center. We analyzed data of all IFIs in children before and after AFP with National Cancer Institute high-risk status who had been started on regimen B induction and regimen B or C consolidation and intensification phases.Results A total of 55 children with high-risk ALL were included in the study. The median age was 4 years, with the majority being between the age of 1 and 10 years (38 out of 55; 65%) and predominantly male (36 out of 55; 69%). Total incidence of IFI in our cohort was 51% (28 out of 55). A significant number of children (16 out of 22 [70%]) who were not on prophylaxis developed IFI versus children (12 out of 33 [28%]) on prophylaxis (p = 0.008). The most common organisms isolated were Candida parapsilosis and Candida tropicalis. Children not receiving AFP were found to be 4.7 times (95% confidence interval: 1.44–15.13) more likely to get IFI than the ones receiving AFP. The presence of concurrent bacterial infection increases the risk of IFI (p = 0.04).Conclusion The incidence of IFI was high in high-risk ALL children who were not on AFP. The introduction of routine AFP reduced the incidence of IFI.

A study on clinical profile of invasive fungal infection in neutropenic children in a tertiary care teaching hospital

Background: Febrile neutropenia is a common complication of anti-cancer chemotherapy. Invasive fungal infections are found mostly after prolonged neutropenia. Early diagnosis and treatment of these infections are of crucial importance. Hence, there is a need to identify the common causative organisms of fungal sepsis in children and our primary objective was to diagnose invasive fungal infections in children of febrile neutropenia and identify the common fungal etiological agents with clinical profile.Methods: This study was done as observational, cross-sectional study for 18 months at the department of microbiology, Lady Hardinge Medical College and department of pediatrics, Kalawati Saran Children’s Hospital. All children less than 18 years of age clinically suspected to have invasive fungal infection with absolute neutrophil count <500 /ml, with fever not responding to antibiotics for more than 3-4 days were included in the study.Results: Hospitalization ≥7 days (100%) was the most common associated risk factor, followed by neutropenia (100%), immunodeficiency (100%), cytotoxic drugs (87.27%) and malignancies (87.27%). Other less commonly associated risk factors were hyperalimentation (23.64%), residence near a construction site (23.64%), presence of urinary catheters (10.91%) and HIV positivity (9.09%). Around 54.54% of sputum samples were positive for fungal culture. A lower positivity was seen in blood culture (14.54%).Conclusions: Candida spp., Aspergillus spp. and Pneumocystis remain the primary fungal pathogens in this patient population. Early clinical suspicion followed by prompt sampling and evaluation for fungal infections may aid in timely diagnosis and reduction of mortality of these patients.

Invasive pulmonary fungal infections in children with severe human adenovirus type 7 pneumonia: A retrospective study.

There has been a rapid increase in the number of human adenovirus type 7 (HAdV-7) and invasive pulmonary fungal infections (IPFIs) co-infection. In this study, we included patients with confirmed HAdV-7 infection during the period from 2018 to 2019 to explore clinical characteristics of severe HAdV-7 pneumonia combined with IPFIs. Among the 143 patients, 35 cases were co-infected with IPFIs. Others were assigned to the control group (n Z 108). Patients wereprone to be complicated with respiratory failure, heart failure and hemophagocytic syndromein IPFIs group. Thirty-one species of fungi were detected in the IPFIs group, among whichAspergillus was the most common species. Compared to control group, patients had lowerlevels of WBC, CD3þ T lymphocyte counts and CD19þ B lymphocyte counts in IPFIs group. Aspergillus is the most common species in IPFIs combined with severe HAdV-7 pneumonia. For children with severe HAdV-7 pneumonia who are younger, have a long course of disease, and have been admitted to the ICU, we should predict the occurrence of IPFIs when there is multi-system dysfunction and the reduction of CD3+ T lymphocyte counts and CD19+ B lymphocyte counts in course of their disease.

Pharmacogenetic Analysis of Voriconazole Treatment in Children.

Voriconazole is among the first-line antifungal drugs to treat invasive fungal infections in children and known for its pronounced inter- and intraindividual pharmacokinetic variability. Polymorphisms in genes involved in the metabolism and transport of voriconazole are thought to influence serum concentrations and eventually the therapeutic outcome. To investigate the impact of these genetic variants and other covariates on voriconazole trough concentrations, we performed a retrospective data analysis, where we used medication data from 36 children suffering from invasive fungal infections treated with voriconazole. Data were extracted from clinical information systems with the new infrastructure SwissPKcdw, and linear mixed effects modelling was performed using R. Samples from 23 children were available for DNA extraction, from which 12 selected polymorphism were genotyped by real-time PCR. 192 (49.1%) of 391 trough serum concentrations measured were outside the recommended range. Voriconazole trough concentrations were influenced by polymorphisms within the metabolizing enzymes CYP2C19 and CYP3A4, and within the drug transporters ABCC2 and ABCG2, as well as by the co-medications ciprofloxacin, levetiracetam, and propranolol. In order to prescribe an optimal drug dosage, pre-emptive pharmacogenetic testing and careful consideration of co-medications in addition to therapeutic drug monitoring might improve voriconazole treatment outcome of children with invasive fungal infections.

Clinical, Laboratory, Radiological, Bronchoscopic, and Outcome Characteristics of Pulmonary Fungal Infection in Children in PICU in Central China: A Case Series.

ObjectiveFungal infections are common in pediatric intensive care units (PICUs), but the monitoring methods are limited. This study analyzed the differences in clinical features, diagnosis, and treatment between PICU patients with and without fungal infection.MethodsThis retrospective study analyzed PICU patients at the Maternal and Child Health Hospital of Hubei Province diagnosed with severe pneumonia between January 2015 and January 2020. The patients were divided into the fungal (F) and non-fungal (NF) infection groups. Levels of 1,3-beta-D-glucan (BDG) and galactomannan (GM) in serum and bronchoalveolar lavage fluid (BALF) were analyzed. Chest computed tomography (CT) images were reviewed.ResultsA total of 357 patients were included. In the F group, fever, moist rales, coarse rales, shortness of breath, and sepsis were more common (all P < 0.05); PICU time, hospitalization duration, and BDG- and GM-positive rates in serum and BALF were all significantly higher than in the NF group (all P < 0.05). The BDG- and GM-positive rates in serum and BALF were higher in the F than in the NF group (all P < 0.05). The abnormal lymphocyte ratios in serum were higher in the F group (all P < 0.05). Wedge-shaped, patchy, streaky shadows and subpleural reticulation were higher in CT images of the F group (all P < 0.05). Tracheobronchial stenosis was more common in pulmonary fibroscopy results of the F group (P = 0.04).ConclusionPICU pneumonia patients with fungal infection have specific clinical and laboratory features compared with those without fungal infection, including higher rates of BALF, serum BDG, GM positivity and tracheobronchial stenosis.

[Raising awareness and practice of invasive pulmonary fungal infections in children].

侵袭性肺部真菌感染是小儿呼吸系统疾病中不容忽视的重要一员，其基础疾病、诊断和防治涉及呼吸、血液、重症监护、感染、免疫和新生儿等多个专业以及影像、检验和临床药学等多个学科。中华医学会儿科学分会和中华儿科杂志编辑委员会组织多学科专家，共同探讨制订了“儿童侵袭性肺部真菌感染临床实践专家共识（2022版）”，对相关的18个临床问题，涵盖基本概念、诊断、治疗和预防等，较全面地给出了目前国内外所确认的建议和说明，以期更精准地指导临床实践。.

[Expert consensus on clinical practice of invasive pulmonary fungal infections in children (2022)].

早期合理规范地诊治侵袭性肺部真菌感染（IPFI）是小儿呼吸病学重要而又紧迫的篇章，IPFI病变呈现在肺部，但其基础疾病、诊断和防治涉及众多学科，中华医学会儿科学分会与中华儿科杂志编辑委员会跨专业学组制订了“儿童侵袭性肺部真菌感染临床实践专家共识（2022版）”，从基本概念、诊断、治疗和预防等方面回答了该领域中迫切需要澄清和认识的18个问题，以期科学地指导与推进儿科学临床实践。.

INVASIVE FUNGAL INFECTIONS IN CHILDREN TREATED FOR HEMATOLOGIC MALIGNANCIES - A FIVE-YEAR SINGLE CENTER EXPERIENCE.

Invasive fungal infections (IFI) are life-threatening complications of intensive chemotherapy treatment, with the incidence in pediatric patients ranging from 2% to 21%. In this article, we describe our 5-year experience of IFI in pediatric oncology patients and its clinical manifestations with radiological findings, treatment and outcome. A retrospective and descriptive survey of IFI in children with hematologic neoplasms was conducted at the Department of Oncology and Hematology, Zagreb Children's Hospital. Medical charts of children 0-17 years of age, of both sexes, treated for leukemias and lymphomas from January 2016 to December 2020 were reviewed. In a 5-year period, 60 patients were treated for hematologic malignancy, acute lymphoblastic leukemia (ALL) being the most prevalent diagnosis. IFI was verified in 9 (15%) children, predominantly in patients with ALL (75%). The specific causative agent was detected in one child, whereas other infections were classified as probable pulmonary aspergillosis. All the patients received standard prophylaxis with fluconazole and treatment with liposomal amphotericin B and voriconazole. The majority of our patients achieved recovery. IFI prevention, diagnosis and treatment remain a challenge. Uniform prophylaxis and therapy protocols, as well as environmental control are of vital importance for the development of better strategies in the prevention, early detection and treatment of IFI in pediatric hematology patients.

A case report on clinical feature, cause and outcome in male pediatric child with cerebral palsy with corpus callosum agenesis with mycosis

Introduction : The most prevalent developmental issue impacting children’s function is cerebral palsy. Brain damage or insult during pregnancy, perinatal, or postnatal periods causes a static, nonprogressive disease. The corpus callosum connects the left and right hemispheres of the brain and is one of the disorders that affect the agenesis of the corpus callosum. The corpus callosum is either absent or substantially absent in ACC. A disruption in brain cell migration during foetal development causes it. Mucormycosis is the third most frequent invasive fungal infection in children, according to recent studies, and its prevalence is increasing. Present complaints and Investigation : A 12-year-old male boy was presented to the hospital with oedema around his eyes, a fever that had been present for three days, respiratory distress, and altered sensorium. He had a history of developmental delay and cerebral palsy. Corpus callosal agenesis is visible on MRI and CT scans of the brain. The lesions have shifted the right orbital muscles. Right eye proptosis is evident. The main diagnosis, therapeutic intervention and outcomes : The doctor diagnosed a case of cerebral palsy with corpus callosal agenesis, retroorbital oedema, and mycosis after a physical examination and inquiry. Vancomycin, MgSO4, and other pharmacological treatments were administered intravenously. For four days, the patient was on CPAP. She received every treatment, but the prognosis was dismal. Her signs and symptoms of respiratory distress were decreased. Conclusion : The thickness of the mid-body of the corpus callosum correlates with the volume of cerebral white matter in children with cerebral palsy and developmental delay, regardless of gestational age or neuromotor outcome.